Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization.

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Tine N Vinther

Full Text Available An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic β-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization to form the structural equivalent of the classical hexamer. The covalently linked dimer neither bound to the insulin receptor, nor induced a metabolic response in vitro. However, it was extremely thermodynamically stable and did not form amyloid fibrils when subjected to mechanical stress, underlining the importance of oligomerization for insulin stability.

DNA repair in B. subtilis: an inducible dimer-specific W-reactivation system

International Nuclear Information System (INIS)

Fields, P.I.; Yasbin, R.E.

1982-01-01

The W-reactivation system of Bacillus subtilis can repair pyrimidine dimers in bacteriophage DNA. This inducible repair system can be activated by treatment of the bacteria with uv, alkylating agents, cross-linking agents and gamma irradiation. However, bacteriophage treated with agents other than those that cause pyrimidine dimers to be produced was not repaired by this unique form of W-reactivation. In contrast, the W-reactivation system of Escherichia coli can repair a variety of damages placed in the bacteriophage DNA

Different β-alanine dimeric forms in trifluoromethanesulfonic acid salts. XRD and vibrational studies

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Wołoszyn, Łukasz; Ilczyszyn, Maria M.

2018-03-01

Two new crystalline salts: β-alaninium trifluoromethanesulfonate (β-AlaOTf) and bis(β-alanine) trifluoromethanesulfonate (β-2AlaOTf) were obtained. The former one contains diprotonated β-alanine dimer, the latter one monoprotonated β-alanine dimer. Both compounds were studied by single crystal XRD, vibrational (IR and Raman) spectroscopy and calorimetric method. The quantum-mechanical calculations (DFT/B3LYP/6-311 ++G(2d,2p)) for the diprotonated dimer were carried out. The β-AlaOTf salt crystallizes in the P 1 bar space group of triclinic system (Z = 2), the β-2AlaOTf in the P21/m space group of monoclinic system (Z = 2). The vibrational data for the studied compounds are discussed in relation to their crystal structure, and provide insight into the character of hydrogen bonds and β-alanine protonation. The studied crystals do not exhibit phase transitions in the solid state.

Serendipitous discovery of light-induced (In Situ) formation of an Azo-bridged dimeric sulfonated naphthol as a potent PTP1B inhibitor.

Science.gov (United States)

Bongard, Robert D; Lepley, Michael; Thakur, Khushabu; Talipov, Marat R; Nayak, Jaladhi; Lipinski, Rachel A Jones; Bohl, Chris; Sweeney, Noreena; Ramchandran, Ramani; Rathore, Rajendra; Sem, Daniel S

2017-05-31

Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results. Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC 50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC 50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5. We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common

(±)-Uncarilins A and B, Dimeric Isoechinulin-Type Alkaloids from Uncaria rhynchophylla.

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Geng, Chang-An; Huang, Xiao-Yan; Ma, Yun-Bao; Hou, Bo; Li, Tian-Ze; Zhang, Xue-Mei; Chen, Ji-Jun

2017-04-28

(±)-Uncarilins A and B (1a/1b and 2a/2b), two pairs of unusual dimeric isoechinulin-type enantiomers with a symmetric four-membered core, were isolated from Uncaria rhynchophylla driven by LCMS-IT-TOF analyses. Their structures were elucidated by extensive 1D and 2D NMR spectra, X-ray diffraction, and ECD spectroscopic data. (-)-Uncarilin B (2a) showed activities on MT 1 and MT 2 receptors with agonistic rates of 11.26% and 52.44% at a concentration of 0.25 mM.

Evolution of magnetization due to asymmetric dimerization: theoretical considerations and application to aberrant oligomers formed by apoSOD1(2SH).

Science.gov (United States)

Sekhar, Ashok; Bain, Alex D; Rumfeldt, Jessica A O; Meiering, Elizabeth M; Kay, Lewis E

2016-02-17

A set of coupled differential equations is presented describing the evolution of magnetization due to an exchange reaction whereby a pair of identical monomers form an asymmetric dimer. In their most general form the equations describe a three-site exchange process that reduces to two-site exchange under certain limiting conditions that are discussed. An application to the study of sparsely populated, transiently formed sets of aberrant dimers, symmetric and asymmetric, of superoxide dismutase is presented. Fits of concentration dependent CPMG relaxation dispersion profiles provide measures of the dimer dissociation constants and both on- and off-rates. Dissociation constants on the order of 70 mM are extracted from fits of the data, with dimeric populations of ∼2% and lifetimes of ∼6 and ∼2 ms for the symmetric and asymmetric complexes, respectively. This work emphasizes the important role that NMR relaxation experiments can play in characterizing very weak molecular complexes that remain invisible to most biophysical approaches.

RelB and RelE of Escherichia coli Form a Tight Complex That Represses Transcription via The Ribbon-Helix-Helix Motif in RelB

DEFF Research Database (Denmark)

Overgaard, Martin; Borch, Jonas; Gerdes, Kenn

2009-01-01

RelB, the Ribbon-Helix-Helix (RHH) repressor encoded by the relBE toxin-antitoxin locus of Escherichia coli, forms a tight complex with RelE and thereby counteracts the mRNA cleavage activity of RelE. In addition, RelB dimers repress the strong relBE promoter and this repression by RelB is enhanced...... by RelE - that is - RelE functions as a transcriptional co-repressor. RelB is a Lon protease substrate and Lon is required both for activation of relBE transcription and for activation of the mRNA cleavage activity of RelE. Here we characterize the molecular interactions important for transcriptional...... motif recognizes four 6 bp repeats within the bipartite binding site. The spacing between each half-site was found to be essential for cooperative interactions between adjacently bound RelB dimers stabilized by the co-repressor RelE. Kinetic and stoichiometric measurements of the interaction between Rel...

Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

DEFF Research Database (Denmark)

Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.

2012-01-01

An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

Monomeric banana lectin at acidic pH overrules conformational stability of its native dimeric form.

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Javed M Khan

Full Text Available Banana lectin (BL is a homodimeric protein categorized among jacalin-related family of lectins. The effect of acidic pH was examined on conformational stability of BL by using circular dichroism, intrinsic fluorescence, 1-anilino-8-napthalene sulfonate (ANS binding, size exclusion chromatography (SEC and dynamic light scattering (DLS. During acid denaturation of BL, the monomerization of native dimeric protein was found at pH 2.0. The elution profile from SEC showed two different peaks (59.65 ml & 87.98 ml at pH 2.0 while single peak (61.45 ml at pH 7.4. The hydrodynamic radii (R h of native BL was 2.9 nm while at pH 2.0 two species were found with R h of 1.7 and 3.7 nm. Furthermore at, pH 2.0 the secondary structures of BL remained unaltered while tertiary structure was significantly disrupted with the exposure of hydrophobic clusters confirming the existence of molten globule like state. The unfolding of BL with different subunit status was further evaluated by urea and temperature mediated denaturation to check their stability. As inferred from high Cm and ΔG values, the monomeric form of BL offers more resistance towards chemical denaturation than the native dimeric form. Besides, dimeric BL exhibited a Tm of 77°C while no loss in secondary structures was observed in monomers even up to 95°C. To the best of our knowledge, this is the first report on monomeric subunit of lectins showing more stability against denaturants than its native dimeric state.

Collisional properties of weakly bound heteronuclear dimers

NARCIS (Netherlands)

Marcelis, B.; Kokkelmans, S.J.J.M.F.; Shlyapnikov, G.V.; Petrov, D.S.

2008-01-01

We consider collisional properties of weakly bound heteronuclear molecules (dimers) formed in a two-species mixture of atoms with a large mass difference. We focus on dimers containing light fermionic atoms as they manifest collisional stability due to an effective dimer-dimer repulsion originating

Core-to-core dimers forming switchable mesophase

Czech Academy of Sciences Publication Activity Database

Horčic, M.; Svoboda, J.; Novotná, Vladimíra; Pociecha, D.; Gorecka, E.

2017-01-01

Roč. 53, č. 18 (2017), s. 2721-2724 ISSN 1359-7345 R&D Projects: GA ČR GA15-02843S Institutional support: RVO:68378271 Keywords : liquid crystals * bent- core mesogens * dimers Subject RIV: JJ - Other Materials OBOR OECD: Nano-materials (production and properties) Impact factor: 6.319, year: 2016

Complex forms of mitochondrial DNA in human B cells transformed by Epstein-Barr virus (EBV)

DEFF Research Database (Denmark)

Christiansen, Gunna; Christiansen, C; Zeuthen, J

1983-01-01

Human lymphocytes and lymphoid cell lines were analyzed for the presence of complex forms of mitochondrial DNA (mtDNA) by electron microscopy. A high frequency (9%-14.5%) of catenated dimers, circular dimers, or oligomers were found in samples from Epstein-Barr-virus-(EBV) transformed lymphoblast......Human lymphocytes and lymphoid cell lines were analyzed for the presence of complex forms of mitochondrial DNA (mtDNA) by electron microscopy. A high frequency (9%-14.5%) of catenated dimers, circular dimers, or oligomers were found in samples from Epstein-Barr-virus-(EBV) transformed...

Mass spectrometric characterization of human serum albumin dimer: A new potential biomarker in chronic liver diseases.

Science.gov (United States)

Naldi, Marina; Baldassarre, Maurizio; Nati, Marina; Laggetta, Maristella; Giannone, Ferdinando Antonino; Domenicali, Marco; Bernardi, Mauro; Caraceni, Paolo; Bertucci, Carlo

2015-08-10

Human serum albumin (HSA) undergoes several structural alterations affecting its properties in pro-oxidant and pro-inflammatory environments, as it occurs during liver cirrhosis. These modifications include the formation of albumin dimers. Although HSA dimers were reported to be an oxidative stress biomarker, to date nothing is known about their role in liver cirrhosis and related complications. Additionally, no high sensitive analytical method was available for HSA dimers assessment in clinical settings. Thus the HSA dimeric form in human plasma was characterized by mass spectrometry using liquid chromatography tandem mass spectrometry (LC-ESI-Q-TOF) and matrix assisted laser desorption time of flight (MALDI-TOF) techniques. N-terminal and C-terminal truncated HSA, as well as the native HSA, undergo dimerization by binding another HSA molecule. This study demonstrated the presence of both homo- and hetero-dimeric forms of HSA. The dimerization site was proved to be at Cys-34, forming a disulphide bridge between two albumin molecules, as determined by LC-MS analysis after tryptic digestion. Interestingly, when plasma samples from cirrhotic subjects were analysed, the dimer/monomer ratio resulted significantly increased when compared to that of healthy subjects. These isoforms could represent promising biomarkers for liver disease. Additionally, this analytical approach leads to the relative quantification of the residual native HSA, with fully preserved structural integrity. Copyright © 2014 Elsevier B.V. All rights reserved.

Calix[4]arene supported clusters: a dimer of [Mn(III)Mn(II)] dimers

DEFF Research Database (Denmark)

Taylor, Stephanie M; McIntosh, Ruaraidh D; Beavers, Christine M

2011-01-01

Phosphinate ligands allow for the transformation of a calix[4]arene supported [Mn(III)(2)Mn(II)(2)] tetramer cluster motif into an unusual [Mn(III)Mn(II)](2) dimer of dimers; the clusters self-assemble in the crystal to form bi-layer arrays reminiscent of the typical packing of calixarene solvates....

Photoreactivation of ultraviolet light-induced damage in cultured fish cells as revealed by increased colony forming ability and decreased content of pyrimidine dimers

International Nuclear Information System (INIS)

Shima, A.; Ikenaga, M.; Egami, N.

1981-01-01

Cultured cells derived from a goldfish were irradiated with 254 nm ultraviolet light. Cell survival and splitting of pyrimidine dimers after photoreactivation treatment with white fluorescent lamps were examined by colony forming ability and by a direct dimer assay, respectively. When UV-irradiated (5 J/m 2 ) cells were illuminated by photoreactivating light, cell survival was enhanced up to a factor of 9(40 min) followed by a decline after prolonged exposures. Exposure of UV-irradiated (15 J/m 2 ) cells to radiation from white fluorescent lamps reduced the amounts of thymine-containing dimers in a photoreactivating fluence dependent manner, up to about 60% reduction at 120 min exposure. Keeping UV-irradiated cells in the dark for up to 120 min did not affect either cell survival or the amount of pyrimidine dimers in DNA, indicating that there were not detectable levels of a dark-repair system in the cells under our conditions. Correlation between photoreactivation of colony forming ability and photoreactivation of the pyrimidine dimers was demonstrated, at least at relatively low fluences of photoreactivating light. (author)

Photoreactivation of ultraviolet light-induced damage in cultured fish cells as revealed by increased colony forming ability and decreased content of pyrimidine dimers

Energy Technology Data Exchange (ETDEWEB)

Shima, A. (Shiga University of Medical Science, Otsu (Japan)); Ikenaga, M. (Osaka Univ. (Japan). Faculty of Medicine); Nikaido, O.; Takebe, H. (Kyoto Univ. (Japan)); Egami, N. (Tokyo Univ. (Japan). Faculty of Science)

1981-03-01

Cultured cells derived from a goldfish were irradiated with 254 nm ultraviolet light. Cell survival and splitting of pyrimidine dimers after photoreactivation treatment with white fluorescent lamps were examined by colony forming ability and by a direct dimer assay, respectively. When UV-irradiated (5 J/m/sup 2/) cells were illuminated by photoreactivating light, cell survival was enhanced up to a factor of 9(40 min) followed by a decline after prolonged exposures. Exposure of UV-irradiated (15 J/m/sup 2/) cells to radiation from white fluorescent lamps reduced the amounts of thymine-containing dimers in a photoreactivating fluence dependent manner, up to about 60% reduction at 120 min exposure. Keeping UV-irradiated cells in the dark for up to 120 min did not affect either cell survival or the amount of pyrimidine dimers in DNA, indicating that there were not detectable levels of a dark-repair system in the cells under our conditions. Correlation between photoreactivation of colony forming ability and photoreactivation of the pyrimidine dimers was demonstrated, at least at relatively low fluences of photoreactivating light.

Atom-dimer scattering in a heteronuclear mixture with a finite intraspecies scattering length

Science.gov (United States)

Gao, Chao; Zhang, Peng

2018-04-01

We study the three-body problem of two ultracold identical bosonic atoms (denoted by B ) and one extra atom (denoted by X ), where the scattering length aB X between each bosonic atom and atom X is resonantly large and positive. We calculate the scattering length aad between one bosonic atom and the shallow dimer formed by the other bosonic atom and atom X , and investigate the effect induced by the interaction between the two bosonic atoms. We find that even if this interaction is weak (i.e., the corresponding scattering length aB B is of the same order of the van der Waals length rvdW or even smaller), it can still induce a significant effect for the atom-dimer scattering length aad. Explicitly, an atom-dimer scattering resonance can always occur when the value of aB B varies in the region with | aB B|≲ rvdW . As a result, both the sign and the absolute value of aad, as well as the behavior of the aad-aB X function, depends sensitively on the exact value of aB B. Our results show that, for a good quantitative theory, the intraspecies interaction is required to be taken into account for this heteronuclear system, even if this interaction is weak.

Dimer monomer transition and dimer re-formation play important role for ATM cellular function during DNA repair

International Nuclear Information System (INIS)

Du, Fengxia; Zhang, Minjie; Li, Xiaohua; Yang, Caiyun; Meng, Hao; Wang, Dong; Chang, Shuang; Xu, Ye; Price, Brendan; Sun, Yingli

2014-01-01

Highlights: • ATM phosphorylates the opposite strand of the dimer in response to DNA damage. • The PETPVFRLT box of ATM plays a key role in its dimer dissociation in DNA repair. • The dephosphorylation of ATM is critical for dimer re-formation after DNA repair. - Abstract: The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair

Hsa-miR-1587 G-quadruplex formation and dimerization induced by NH4+, molecular crowding environment and jatrorrhizine derivatives.

Science.gov (United States)

Tan, Wei; Yi, Long; Zhu, Zhentao; Zhang, Lulu; Zhou, Jiang; Yuan, Gu

2018-03-01

A guanine-rich human mature microRNA, miR-1587, was discovered to form stable intramolecular G-quadruplexes in the presence of K + , Na + and low concentration of NH 4 + (25mM) by electrospray ionization mass spectrometry (ESI-MS) combined with circular dichroism (CD) spectroscopy. Furthermore, under high concentration of NH 4 + (100mM) or molecular crowding environments, miR-1587 formed a dimeric G-quadruplex through 3'-to-3' stacking of two monomeric G-quadruplex subunits with one ammonium ion sandwiched between the interfaces. Specifically, two synthesized jatrorrhizine derivatives with terminal amine groups could also induce the dimerization of miR-1587 G-quadruplex and formed 1:1 and 2:1 complexes with the dimeric G-quadruplex. In contrast, jatrorrhizine could bind with the dimeric miR-1587 G-quadruplex, but could not induce dimerization of miR-1587 G-quadruplex. These results provide a new strategy to regulate the functions of miR-1587 through induction of G-quadruplex formation and dimerization. Copyright © 2017 Elsevier B.V. All rights reserved.

Jozilebomines A and B, Naphthylisoquinoline Dimers from the Congolese Liana Ancistrocladus ileboensis, with Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Cell Line.

Science.gov (United States)

Li, Jun; Seupel, Raina; Bruhn, Torsten; Feineis, Doris; Kaiser, Marcel; Brun, Reto; Mudogo, Virima; Awale, Suresh; Bringmann, Gerhard

2017-10-27

Two new naphthylisoquinoline dimers, jozilebomines A (1a) and B (1b), were isolated from the roots of the Congolese plant Ancistrocladus ileboensis, along with the known dimer jozimine A 2 (2). These compounds are Dioncophyllaceae-type metabolites, i.e., lacking oxygen functions at C-6 and with an R-configuration at C-3 in their tetrahydroisoquinoline moieties. The dimers 1a and 1b consist of two 7,1'-coupled naphthylisoquinoline monomers linked through an unprecedented 3',6″-coupling in the binaphthalene core and not, as in 2, via the C-3-positions of the two naphthalene units. Thus, different from the C 2 -symmetric jozimine A 2 (2), the new jozilebomines are constitutionally unsymmetric. The central biaryl axis of each of the three dimers is rotationally hindered, so that 1a, 1b, and 2 possess three consecutive chiral axes. The two jozilebomines have identical constitutions and the same absolute configurations at all four stereogenic centers, but differ from each other in their axial chirality. Their structural elucidation was achieved by HRESIMS, 1D and 2D NMR, oxidative degradation, and experimental and calculated ECD data. They exhibited distinct and specific antiplasmodial activities. All dimers showed potent cytotoxicity against HeLa human cervical cancer cells and preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions. Furthermore, these dimers significantly inhibited the colony formation of PANC-1 cells, even when exposed to noncytotoxic concentration for a short time. Jozilebomines A (1a) and B (1b) and jozimine A 2 (2) represent novel potential candidates for future drug development against pancreatic cancer.

Dimeric Structure of the Blue Light Sensor Protein Photozipper in the Active State.

Science.gov (United States)

Ozeki, Kohei; Tsukuno, Hiroyuki; Nagashima, Hiroki; Hisatomi, Osamu; Mino, Hiroyuki

2018-02-06

The light oxygen voltage-sensing (LOV) domain plays a crucial role in blue light (BL) sensing in plants and microorganisms. LOV domains are usually associated with the effector domains and regulate the activities of effector domains in a BL-dependent manner. Photozipper (PZ) is monomeric in the dark state. BL induces reversible dimerization of PZ and subsequently increases its affinity for the target DNA sequence. In this study, we report the analyses of PZ by pulsed electron-electron double resonance (PELDOR). The neutral flavin radical was formed by BL illumination in the presence of dithiothreitol in the LOV-C254S (without the bZIP domain) and PZ-C254S mutants, where the cysteine residue responsible for adduct formation was replaced with serine. The magnetic dipole interactions of 3 MHz between the neutral radicals were detected in both LOV-C254S and PZ-C254S, indicating that these mutants are dimeric in the radical state. The PELDOR simulation showed that the distance between the radical pair is close to that estimated from the dimeric crystal structure in the "light state" [Heintz, U., and Schlichting, I. (2016) eLife 5, e11860], suggesting that in the radical state, LOV domains in PZ-C254S form a dimer similar to that of LOV-C254S, which lacks the bZIP domain.

Study of molybdenum(VI) dimerization equilibrium in strongly acidic medium

International Nuclear Information System (INIS)

Esbelin, E.

2000-01-01

Molybdenum (VI) was investigated spectro-photometrically in non complexing and strongly acidic medium for the first time by Krumenacker. Cationic species of molybdenum were identified by electrophoresis on cellulose paper in highly acidic solutions. From these early results using absorption spectrophotometry, Krumenacker postulated the condensation of molybdenum in this medium. He studied the polymeric species by measuring diffusion coefficients and identified the polymeric form as a dimer. He described the system by equations (1) and (2). Cruywagen later added two equations (3) and (4) to supplement the description of the system. The aim of this work was to re-examine the conditional dimerization equilibrium between the various species of molybdenum(VI) in strongly acid medium by focussing on the influence of the medium. All Mo solution concentrations were analyzed by ICP-AES. Absorbance of the solutions were measured with a VARIAN model CARY5 spectrophotometer in double beam mode with air as reference; blank solutions contained all reagents except molybdenum. The quartz cell path length was 1 mm. The dimerization of monomeric molybdenum(VI) was investigated spectro-photometrically at perchloric acid concentrations of 0.5, 1.0, 2.0 and 3 M at 25 deg C. Two absorption bands at 215 and 245 nm were observed and attributed to monomeric and dimeric forms respectively. The variations in the conditional molar absorption coefficient of molybdenum with total molybdenum(VI) concentration is indicative of several molybdenum forms involved in the total absorbance. Dimerization equilibrium is defined by equation (5). By using the additivity of absorbance and mass conservation of molybdenum, a descriptive equation of the 'spectrochemical' system is developed. This equation is linearized into two forms (6) et (7). From them, two refinement methods were used to estimate the conditional dimerization constant K' d for various medium concentrations. This numerical procedure offers

Mapping local structural perturbations in the native state of stefin B (cystatin B under amyloid forming conditions

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Robert eParamore

2012-10-01

Full Text Available Unlike a number of amyloid-forming proteins, stefins, in particular stefin B (cystatin B form amyloids under conditions where the native state predominates. In order to trigger oligomerization processes, the stability of the protein needs to be compromised, favoring structural re-arrangement however, accelerating fibril formation is not a simple function of protein stability. We report here on how optimal conditions for amyloid formation lead to the destabilization of dimeric and tetrameric states of the protein in favor of the monomer. Small, highly localized structural changes can be mapped out that allow us to visualize directly areas of the protein which eventually become responsible for triggering amyloid formation. These regions of the protein overlap with the Cu (II-binding sites which we identify here for the first time. We hypothesize that in vivo modulators of amyloid formation may act similarly to painstakingly optimized solvent conditions developed in vitro. We discuss these data in the light of current structural models of stefin B amyloid fibrils based on H-exchange data, where the detachment of the helical part and the extension of loops were observed.

Structure of 1,5-Anhydro-D-Fructose: X-ray Analysis of Crystalline Acetylated Dimeric Forms

DEFF Research Database (Denmark)

Lundt, Inge; Andersen, Søren Møller; Marcussen, Jan

1998-01-01

Acetylation of 1,5-anhydro-D-fructose under acidic conditions gave two crystalline acetylated dimeric forms, which by X-ray analysis were shown to be diastereomeric spiroketals formed between C-2 and C-2´/C-3´. The structures of the compounds differed only at the configuration at C-2. Acetylation...... or benzoylation of 1,5-anhydro-D-fructose in pyridine yielded 3,6-di-O-acetyl-1,5-anhydro-4-deoxy-D-glycero-hex-3-enos-2-ulopyra -nose or crystalline 1,5-anhydro-3,6-di-O-benzoyl-4-deoxy-D-glycero-hex-3-enos-2-ulo-py ranose....

A novel form of the RelA nuclear factor kappaB subunit is induced by and forms a complex with the proto-oncogene c-Myc.

Science.gov (United States)

Chapman, Neil R; Webster, Gill A; Gillespie, Peter J; Wilson, Brian J; Crouch, Dorothy H; Perkins, Neil D

2002-01-01

Members of both Myc and nuclear factor kappaB (NF-kappaB) families of transcription factors are found overexpressed or inappropriately activated in many forms of human cancer. Furthermore, NF-kappaB can induce c-Myc gene expression, suggesting that the activities of these factors are functionally linked. We have discovered that both c-Myc and v-Myc can induce a previously undescribed, truncated form of the RelA(p65) NF-kappaB subunit, RelA(p37). RelA(p37) encodes the N-terminal DNA binding and dimerization domain of RelA(p65) and would be expected to function as a trans-dominant negative inhibitor of NF-kappaB. Surprisingly, we found that RelA(p37) no longer binds to kappaB elements. This result is explained, however, by the observation that RelA(p37), but not RelA(p65), forms a high-molecular-mass complex with c-Myc. These results demonstrate a previously unknown functional and physical interaction between RelA and c-Myc with many significant implications for our understanding of the role that both proteins play in the molecular events underlying tumourigenesis. PMID:12027803

The export receptor Crm1 forms a dimer to promote nuclear export of HIV RNA.

Science.gov (United States)

Booth, David S; Cheng, Yifan; Frankel, Alan D

2014-12-08

The HIV Rev protein routes viral RNAs containing the Rev Response Element (RRE) through the Crm1 nuclear export pathway to the cytoplasm where viral proteins are expressed and genomic RNA is delivered to assembling virions. The RRE assembles a Rev oligomer that displays nuclear export sequences (NESs) for recognition by the Crm1-Ran(GTP) nuclear receptor complex. Here we provide the first view of an assembled HIV-host nuclear export complex using single-particle electron microscopy. Unexpectedly, Crm1 forms a dimer with an extensive interface that enhances association with Rev-RRE and poises NES binding sites to interact with a Rev oligomer. The interface between Crm1 monomers explains differences between Crm1 orthologs that alter nuclear export and determine cellular tropism for viral replication. The arrangement of the export complex identifies a novel binding surface to possibly target an HIV inhibitor and may point to a broader role for Crm1 dimerization in regulating host gene expression.

Phase behaviour of heteronuclear dimers in three-dimensional systems-a Monte Carlo study

International Nuclear Information System (INIS)

Rzysko, W; Binder, K

2008-01-01

Monte Carlo simulation in the grand canonical ensemble, the histogram reweighting technique and finite size scaling are used to study the phase behaviour of dimers in three-dimensional systems. A single molecule is composed of two segments A and B, and the bond between them cannot be broken. The phase diagrams have been estimated for a set of model systems. Different structures formed by heteronuclear dimers have been found. The results show a great variety of vapour-liquid coexistence behaviour depending on the strength of the interactions between segments

Multiple regions of Harvey sarcoma virus RNA can dimerize in vitro.

Science.gov (United States)

Feng, Y X; Fu, W; Winter, A J; Levin, J G; Rein, A

1995-04-01

Retroviruses contain a dimeric RNA consisting of two identical molecules of plus-strand genomic RNA. The structure of the linkage between the two monomers is not known, but they are believed to be joined near their 5' ends. Darlix and coworkers have reported that transcripts of retroviral RNA sequences can dimerize spontaneously in vitro (see, for example, E. Bieth, C. Gabus, and J. L. Darlix, Nucleic Acids Res. 18:119-127, 1990). As one approach to identification of sequences which might participate in the linkage, we have mapped sequences derived from the 5' 378 bases of Harvey sarcoma virus (HaSV) RNA which can dimerize in vitro. We found that at least three distinct regions, consisting of nucleotides 37 to 229, 205 to 272, and 271 to 378, can form these dimers. Two of these regions contain nucleotides 205 to 226; computer analysis suggests that this region can form a stem-loop with an inverted repeat in the loop. We propose that this hypothetical structure is involved in dimer formation by these two transcripts. We also compared the thermal stabilities of each of these dimers with that of HaSV viral RNA. Dimers of nucleotides 37 to 229 and 205 to 272 both exhibited melting temperatures near that of viral RNA, while dimers of nucleotides 271 to 378 are quite unstable. We also found that dimers of nucleotides 37 to 378 formed at 37 degrees C are less thermostable than dimers of the same RNA formed at 55 degrees C. It seems possible that bases from all of these regions participate in the dimer linkage present in viral RNA.

Solid state NMR sequential resonance assignments and conformational analysis of the 2x10.4 kDa dimeric form of the Bacillus subtilis protein Crh

Energy Technology Data Exchange (ETDEWEB)

Boeckmann, Anja [Institut de Biologie et Chimie des Proteines, C.N.R.S UMR 5086 (France)], E-mail: a.bockmann@ibcp.fr; Lange, Adam [Max-Planck-Institute for Biophysical Chemistry, Solid-state NMR (Germany); Galinier, Anne [Institut de Biologie Structurale et Microbiologie, C.N.R.S UPR 9043 (France); Luca, Sorin [Max-Planck-Institute for Biophysical Chemistry, Solid-state NMR (Germany); Giraud, Nicolas; Juy, Michel [Institut de Biologie et Chimie des Proteines, C.N.R.S UMR 5086 (France); Heise, Henrike [Max-Planck-Institute for Biophysical Chemistry, Solid-state NMR (Germany); Montserret, Roland; Penin, Francois [Institut de Biologie et Chimie des Proteines, C.N.R.S UMR 5086 (France); Baldus, Marc [Max-Planck-Institute for Biophysical Chemistry, Solid-state NMR (Germany)], E-mail: maba@mpibpc.mpg.de

2003-12-15

Solid state NMR sample preparation and resonance assignments of the U-[{sup 13}C,{sup 15}N] 2x10.4 kDa dimeric form of the regulatory protein Crh in microcrystalline, PEG precipitated form are presented. Intra- and interresidue correlations using dipolar polarization transfer methods led to nearly complete sequential assignments of the protein, and to 88% of all {sup 15}N, {sup 13}C chemical shifts. For several residues, the resonance assignments differ significantly from those reported for the monomeric form analyzed by solution state NMR. Dihedral angles obtained from a TALOS-based statistical analysis suggest that the microcrystalline arrangement of Crh must be similar to the domain-swapped dimeric structure of a single crystal form recently solved using X-ray crystallography. For a limited number of protein residues, a remarkable doubling of the observed NMR resonances is observed indicative of local static or dynamic conformational disorder. Our study reports resonance assignments for the largest protein investigated by solid state NMR so far and describes the conformational dimeric variant of Crh with previously unknown chemical shifts.

Bovine nucleus caudatus acetylcholinesterase: active site determination and investigation of a dimeric form obtained by selective proteolysis

Energy Technology Data Exchange (ETDEWEB)

Landauer, P.; Ruess, K.P.; Lieflaender, M.

1984-09-01

The number of catalytic subunits of purified bovine nucleus caudatus acetylcholinesterase (E.C. 3.1.1.7) has been determined by active site labelling with (3H)diisopropyl fluorophosphate ((3H)DFP). The 10.5 S, 16 S, and 20 S forms were estimated to contain two, four, and six active sites, respectively, per molecule. A 4.8 S form, which showed a weak amphiphile-dependent activity behavior, was obtained by selective proteolytic digestion with pronase. The inability of the purified 4.8 S form to aggregate after detergent removal, and the molecular mass in the range of 130-165 kD under nondenaturating conditions, indicate that this form is a dimeric form, lacking those hydrophobic regions responsible for aggregation.

How different is the borazine-acetylene dimer from the benzene-acetylene dimer? A matrix isolation infrared and ab initio quantum chemical study

Science.gov (United States)

Verma, Kanupriya; Viswanathan, K. S.; Majumder, Moumita; Sathyamurthy, N.

2017-11-01

The 1:1 dimer of borazine-acetylene has been studied for the first time, both experimentally and computationally. The borazine-acetylene dimer was trapped in Ar and N2 matrices, and studied using infrared spectroscopy. Our experiments clearly revealed two isomers of the borazine-acetylene complex, one in which the N-H of borazine interacted with the carbon of acetylene, and another in which the C-H of acetylene formed a hydrogen bond with a nitrogen atom of borazine. The formation of both isomers in the matrix was evidenced by shifts in the vibrational frequencies of the appropriate modes. Reassuringly, the experimental observations were corroborated by our computations using the second-order Møller-Plesset perturbation theoretic method and coupled-cluster singles, doubles and perturbative triples method in conjunction with different Dunning basis sets, which indicated both these isomers to be stable minima, with the N-HṡṡṡC complex being the global minimum. Atoms-in-molecules and energy decomposition analysis were also carried out for the different isomers of the dimer. These studies reveal that replacing the three C-C linkages in benzene with three B-N linkages in borazine modifies the interaction in the dimer sufficiently, to result in a different potential energy landscape for the borazine-acetylene system when compared with the benzene-acetylene system.

Structural insights into lipid-dependent reversible dimerization of human GLTP

International Nuclear Information System (INIS)

Samygina, Valeria R.; Ochoa-Lizarralde, Borja; Popov, Alexander N.; Cabo-Bilbao, Aintzane; Goni-de-Cerio, Felipe; Molotkovsky, Julian G.; Patel, Dinshaw J.; Brown, Rhoderick E.; Malinina, Lucy

2013-01-01

It is shown that dimerization is promoted by glycolipid binding to human GLTP. The importance of dimer flexibility in wild-type protein is manifested by point mutation that ‘locks’ the dimer while diversifying ligand/protein adaptations. Human glycolipid transfer protein (hsGLTP) forms the prototypical GLTP fold and is characterized by a broad transfer selectivity for glycosphingolipids (GSLs). The GLTP mutation D48V near the ‘portal entrance’ of the glycolipid binding site has recently been shown to enhance selectivity for sulfatides (SFs) containing a long acyl chain. Here, nine novel crystal structures of hsGLTP and the SF-selective mutant complexed with short-acyl-chain monoSF and diSF in different crystal forms are reported in order to elucidate the potential functional roles of lipid-mediated homodimerization. In all crystal forms, the hsGLTP–SF complexes displayed homodimeric structures supported by similarly organized intermolecular interactions. The dimerization interface always involved the lipid sphingosine chain, the protein C-terminus (C-end) and α-helices 6 and 2, but the D48V mutant displayed a ‘locked’ dimer conformation compared with the hinge-like flexibility of wild-type dimers. Differences in contact angles, areas and residues at the dimer interfaces in the ‘flexible’ and ‘locked’ dimers revealed a potentially important role of the dimeric structure in the C-end conformation of hsGLTP and in the precise positioning of the key residue of the glycolipid recognition centre, His140. ΔY207 and ΔC-end deletion mutants, in which the C-end is shifted or truncated, showed an almost complete loss of transfer activity. The new structural insights suggest that ligand-dependent reversible dimerization plays a role in the function of human GLTP

A Phytophthora sojae effector PsCRN63 forms homo-/hetero-dimers to suppress plant immunity via an inverted association manner.

Science.gov (United States)

Li, Qi; Zhang, Meixiang; Shen, Danyu; Liu, Tingli; Chen, Yanyu; Zhou, Jian-Min; Dou, Daolong

2016-05-31

Oomycete pathogens produce a large number of effectors to promote infection. Their mode of action are largely unknown. Here we show that a Phytophthora sojae effector, PsCRN63, suppresses flg22-induced expression of FRK1 gene, a molecular marker in pathogen-associated molecular patterns (PAMP)-triggered immunity (PTI). However, PsCRN63 does not suppress upstream signaling events including flg22-induced MAPK activation and BIK1 phosphorylation, indicating that it acts downstream of MAPK cascades. The PsCRN63-transgenic Arabidopsis plants showed increased susceptibility to bacterial pathogen Pseudomonas syringae pathovar tomato (Pst) DC3000 and oomycete pathogen Phytophthora capsici. The callose deposition were suppressed in PsCRN63-transgenic plants compared with the wild-type control plants. Genes involved in PTI were also down-regulated in PsCRN63-transgenic plants. Interestingly, we found that PsCRN63 forms an dimer that is mediated by inter-molecular interactions between N-terminal and C-terminal domains in an inverted association manner. Furthermore, the N-terminal and C-terminal domains required for the dimerization are widely conserved among CRN effectors, suggesting that homo-/hetero-dimerization of Phytophthora CRN effectors is required to exert biological functions. Indeed, the dimerization was required for PTI suppression and cell death-induction activities of PsCRN63.

Microwave measurements of the tropolone–formic acid doubly hydrogen bonded dimer

Energy Technology Data Exchange (ETDEWEB)

Pejlovas, Aaron M.; Kukolich, Stephen G. [Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721 (United States); Serrato, Agapito; Lin, Wei [Department of Chemistry, University of Texas Rio Grande Valley, Brownsville, Texas 78520 (United States)

2016-01-28

The microwave spectrum was measured for the doubly hydrogen bonded dimer formed between tropolone and formic acid. The predicted symmetry of this dimer was C{sub 2v}(M), and it was expected that the concerted proton tunneling motion would be observed. After measuring 25 a- and b-type rotational transitions, no splittings which could be associated with a concerted double proton tunneling motion were observed. The calculated barrier to the proton tunneling motion is near 15 000 cm{sup −1}, which would likely make the tunneling frequencies too small to observe in the microwave spectra. The rotational and centrifugal distortion constants determined from the measured transitions were A = 2180.7186(98) MHz, B = 470.873 90(25) MHz, C = 387.689 84(22) MHz, D{sub J} = 0.0100(14) kHz, D{sub JK} = 0.102(28) kHz, and D{sub K} = 13.2(81) kHz. The B3LYP/aug-cc-pVTZ calculated rotational constants were within 1% of the experimentally determined values.

A discotic triphenylene dimer as organic hole transporting material for electroluminescence devices

International Nuclear Information System (INIS)

Mao Huaxiang; He Zhiqun; Wang Junling; Zhang Chunxiu; Xie, Ping; Zhang Rongben

2007-01-01

A triphenylene dimer, an intermediate between a discotic triphenylene molecule and the macromolecule, had been prepared by linking together two triphenylene units via phenylene carbamate linkages, which was formed through a reaction between one 1,4-phenylene diisocyanate and two hydroxyl end groups on flexible substituents of triphenylenes. The dimer exhibited good film-forming property. Its temperature-dependent phase transitions were investigated using differential scanning calorimetry and polarized optical microscopy. Room temperature microstructure of the dimer was analyzed by X-ray diffraction. Charge mobility of the triphenylene dimer was also measured. Our preliminary result using the materials in a sandwich light-emitting device is reported here. It demonstrates that the triphenylene dimer is a promising candidate as a hole transporting material

Tor forms a dimer through an N-terminal helical solenoid with a complex topology

Science.gov (United States)

Baretić, Domagoj; Berndt, Alex; Ohashi, Yohei; Johnson, Christopher M.; Williams, Roger L.

2016-04-01

The target of rapamycin (Tor) is a Ser/Thr protein kinase that regulates a range of anabolic and catabolic processes. Tor is present in two complexes, TORC1 and TORC2, in which the Tor-Lst8 heterodimer forms a common sub-complex. We have determined the cryo-electron microscopy (EM) structure of Tor bound to Lst8. Two Tor-Lst8 heterodimers assemble further into a dyad-symmetry dimer mediated by Tor-Tor interactions. The first 1,300 residues of Tor form a HEAT repeat-containing α-solenoid with four distinct segments: a highly curved 800-residue N-terminal 'spiral', followed by a 400-residue low-curvature 'bridge' and an extended `railing' running along the bridge leading to the 'cap' that links to FAT region. This complex topology was verified by domain insertions and offers a new interpretation of the mTORC1 structure. The spiral of one TOR interacts with the bridge of another, which together form a joint platform for the Regulatory Associated Protein of TOR (RAPTOR) regulatory subunit.

Structural insights into the intertwined dimer of fyn SH2.

Science.gov (United States)

Huculeci, Radu; Garcia-Pino, Abel; Buts, Lieven; Lenaerts, Tom; van Nuland, Nico

2015-12-01

Src homology 2 domains are interaction modules dedicated to the recognition of phosphotyrosine sites incorporated in numerous proteins found in intracellular signaling pathways. Here we provide for the first time structural insight into the dimerization of Fyn SH2 both in solution and in crystalline conditions, providing novel crystal structures of both the dimer and peptide-bound structures of Fyn SH2. Using nuclear magnetic resonance chemical shift analysis, we show how the peptide is able to eradicate the dimerization, leading to monomeric SH2 in its bound state. Furthermore, we show that Fyn SH2's dimer form differs from other SH2 dimers reported earlier. Interestingly, the Fyn dimer can be used to construct a completed dimer model of Fyn without any steric clashes. Together these results extend our understanding of SH2 dimerization, giving structural details, on one hand, and suggesting a possible physiological relevance of such behavior, on the other hand. © 2015 The Protein Society.

Glycine transporter dimers: evidence for occurrence in the plasma membrane.

Science.gov (United States)

Bartholomäus, Ingo; Milan-Lobo, Laura; Nicke, Annette; Dutertre, Sébastien; Hastrup, Hanne; Jha, Alok; Gether, Ulrik; Sitte, Harald H; Betz, Heinrich; Eulenburg, Volker

2008-04-18

Different Na(+)/Cl(-)-dependent neurotransmitter transporters of the SLC6a family have been shown to form dimers or oligomers in both intracellular compartments and at the cell surface. In contrast, the glycine transporters (GlyTs) GlyT1 and -2 have been reported to exist as monomers in the plasma membrane based on hydrodynamic and native gel electrophoretic studies. Here, we used cysteine substitution and oxidative cross-linking to show that of GlyT1 and GlyT2 also form dimeric complexes within the plasma membrane. GlyT oligomerization at the cell surface was confirmed for both GlyT1 and GlyT2 by fluorescence resonance energy transfer microscopy. Endoglycosidase treatment and surface biotinylation further revealed that complex-glycosylated GlyTs form dimers located at the cell surface. Furthermore, substitution of tryptophan 469 of GlyT2 by an arginine generated a transporter deficient in dimerization that was retained intracellulary. Based on these results and GlyT structures modeled by using the crystal structure of the bacterial homolog LeuT(Aa), as a template, residues located within the extracellular loop 3 and at the beginning of transmembrane domain 6 are proposed to contribute to the dimerization interface of GlyTs.

Effects of Dimerization of Serratia marcescens Endonuclease on Water Dynamics.

Energy Technology Data Exchange (ETDEWEB)

Chen, Chuanying; Beck, Brian W.; Krause, Kurt; Weksberg, Tiffany E.; Pettitt, Bernard M.

2007-02-15

The research described in this product was performed in part in the Environmental Molecular Sciences Laboratory, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. The dynamics and structure of Serratia marcescens endonuclease and its neighboring solvent are investigated by molecular dynamics (MD). Comparisons are made with structural and biochemical experiments. The dimer form is physiologic and functions more processively than the monomer. We previously found a channel formed by connected clusters of waters from the active site to the dimer interface. Here, we show that dimerization clearly changes correlations in the water structure and dynamics in the active site not seen in the monomer. Our results indicate that water at the active sites of the dimer is less affected compared with bulk solvent than in the monomer where it has much slower characteristic relaxation times. Given that water is a required participant in the reaction, this gives a clear advantage to dimerization in the absence of an apparent ability to use both active sites simultaneously.

Base Pair Opening in a Deoxynucleotide Duplex Containing a cis-syn Thymine Cyclobutane Dimer Lesion

Science.gov (United States)

Wenke, Belinda B.; Huiting, Leah N.; Frankel, Elisa B.; Lane, Benjamin F.; Núñez, Megan E.

2014-01-01

The cis-syn thymine cyclobutane dimer is a DNA photoproduct implicated in skin cancer. We compared the stability of individual base pairs in thymine dimer-containing duplexes to undamaged parent 10-mer duplexes. UV melting thermodynamic measurements, CD spectroscopy, and 2D NOESY NMR spectroscopy confirm that the thymine dimer lesion is locally and moderately destabilizing within an overall B-form duplex conformation. We measured the rates of exchange of individual imino protons by NMR using magnetization transfer from water and determined the equilibrium constant for the opening of each base pair Kop. In the normal duplex Kop decreases from the frayed ends of the duplex toward the center, such that the central TA pair is the most stable with a Kop of 8×10−7. In contrast, base pair opening at the 5’T of the thymine dimer is facile. The 5’T of the dimer has the largest equilibrium constant (Kop =3×10−4) in its duplex, considerably larger than even the frayed penultimate base pairs. Notably, base pairing by the 3’T of the dimer is much more stable than by the 5’T, indicating that the predominant opening mechanism for the thymine dimer lesion is not likely to be flipping out into solution as a single unit. The dimer asymmetrically affects the stability of the duplex in its vicinity, destabilizing base pairing on its 5’ side more than on the 3’ side. The striking differences in base pair opening between parent and dimer duplexes occur independently of the duplex-single strand melting transitions. PMID:24328089

Subsurface dimerization in III-V semiconductor (001) surfaces

DEFF Research Database (Denmark)

Kumpf, C.; Marks, L.D.; Ellis, D.

2001-01-01

We present the atomic structure of the c(8 X 2) reconstructions of InSb-, InAs-, and GaAs-(001) surfaces as determined by surface x-ray diffraction using direct methods. Contrary to common belief, group III dimers are not prominent on the surface, instead subsurface dimerization of group m atoms ...... takes place in the second bilayer, accompanied by a major rearrangement of the surface atoms above the dimers to form linear arrays. By varying the occupancies of four surface sites the (001)-c(8 X 2) reconstructions of III-V semiconductors can be described in a unified model....

The Rate of Vitamin A Dimerization in Lipofuscinogenesis, Fundus Autofluorescence, Retinal Senescence and Degeneration.

Science.gov (United States)

Washington, Ilyas; Saad, Leonide

2016-01-01

One of the earliest events preceding several forms of retinal degeneration is the formation and accumulation of vitamin A dimers in the retinal pigment epithelium (RPE) and underlying Bruch's membrane (BM). Such degenerations include Stargardt disease, Best disease, forms of retinitis pigmentosa, and age-related macular degeneration (AMD). Since their discovery in the 1990's, dimers of vitamin A, have been postulated as chemical triggers driving retinal senescence and degeneration. There is evidence to suggest that the rate at which vitamin A dimerizes and the eye's response to the dimerization products may dictate the retina's lifespan. Here, we present outstanding questions, finding the answers to which may help to elucidate the role of vitamin A dimerization in retinal degeneration.

Dimerization of translationally controlled tumor protein is essential for its cytokine-like activity.

Directory of Open Access Journals (Sweden)

Miyoung Kim

Full Text Available BACKGROUND: Translationally Controlled Tumor Protein (TCTP found in nasal lavage fluids of allergic patients was named IgE-dependent histamine-releasing factor (HRF. Human recombinant HRF (HrHRF has been recently reported to be much less effective than HRF produced from activated mononuclear cells (HRFmn. METHODS AND FINDINGS: We found that only NH(2-terminal truncated, but not C-terminal truncated, TCTP shows cytokine releasing activity compared to full-length TCTP. Interestingly, only NH(2-terminal truncated TCTP, unlike full-length TCTP, forms dimers through intermolecular disulfide bonds. We tested the activity of dimerized full-length TCTP generated by fusing it to rabbit Fc region. The untruncated-full length protein (Fc-HrTCTP was more active than HrTCTP in BEAS-2B cells, suggesting that dimerization of TCTP, rather than truncation, is essential for the activation of TCTP in allergic responses. We used confocal microscopy to evaluate the affinity of TCTPs to its putative receptor. We detected stronger fluorescence in the plasma membrane of BEAS-2B cells incubated with Del-N11TCTP than those incubated with rat recombinant TCTP (RrTCTP. Allergenic activity of Del-N11TCTP prompted us to see whether the NH(2-terminal truncated TCTP can induce allergic airway inflammation in vivo. While RrTCTP had no influence on airway inflammation, Del-N11TCTP increased goblet cell hyperplasia in both lung and rhinal cavity. The dimerized protein was found in sera from allergic patients, and bronchoalveolar lavage fluids from airway inflamed mice. CONCLUSIONS: Dimerization of TCTP seems to be essential for its cytokine-like activity. Our study has potential to enhance the understanding of pathogenesis of allergic disease and provide a target for allergic drug development.

Peptides Interfering 3A Protein Dimerization Decrease FMDV Multiplication.

Directory of Open Access Journals (Sweden)

Mónica González-Magaldi

Full Text Available Nonstructural protein 3A is involved in relevant functions in foot-and-mouth disease virus (FMDV replication. FMDV 3A can form homodimers and preservation of the two hydrophobic α-helices (α1 and α2 that stabilize the dimer interface is essential for virus replication. In this work, small peptides mimicking residues involved in the dimer interface were used to interfere with dimerization and thus gain insight on its biological function. The dimer interface peptides α1, α2 and that spanning the two hydrophobic α-helices, α12, impaired in vitro dimer formation of a peptide containing the two α-helices, this effect being higher with peptide α12. To assess the effect of dimer inhibition in cultured cells, the interfering peptides were N-terminally fused to a heptaarginine (R7 sequence to favor their intracellular translocation. Thus, when fused to R7, interference peptides (100 μM were able to inhibit dimerization of transiently expressed 3A, the higher inhibitions being found with peptides α1 and α12. The 3A dimerization impairment exerted by the peptides correlated with significant, specific reductions in the viral yield recovered from peptide-treated FMDV infected cells. In this case, α2 was the only peptide producing significant reductions at concentrations lower than 100 μM. Thus, dimer interface peptides constitute a tool to understand the structure-function relationship of this viral protein and point to 3A dimerization as a potential antiviral target.

Disulfide-mediated stabilization of the IκB kinase binding domain of NF-κB essential modulator (NEMO).

Science.gov (United States)

Zhou, Li; Yeo, Alan T; Ballarano, Carmine; Weber, Urs; Allen, Karen N; Gilmore, Thomas D; Whitty, Adrian

2014-12-23

Human NEMO (NF-κB essential modulator) is a 419 residue scaffolding protein that, together with catalytic subunits IKKα and IKKβ, forms the IκB kinase (IKK) complex, a key regulator of NF-κB pathway signaling. NEMO is an elongated homodimer comprising mostly α-helix. It has been shown that a NEMO fragment spanning residues 44-111, which contains the IKKα/β binding site, is structurally disordered in the absence of bound IKKβ. Herein we show that enforcing dimerization of NEMO1-120 or NEMO44-111 constructs through introduction of one or two interchain disulfide bonds, through oxidation of the native Cys54 residue and/or at position 107 through a Leu107Cys mutation, induces a stable α-helical coiled-coil structure that is preorganized to bind IKKβ with high affinity. Chemical and thermal denaturation studies showed that, in the context of a covalent dimer, the ordered structure was stabilized relative to the denatured state by up to 3 kcal/mol. A full-length NEMO-L107C protein formed covalent dimers upon treatment of mammalian cells with H2O2. Furthermore, NEMO-L107C bound endogenous IKKβ in A293T cells, reconstituted TNF-induced NF-κB signaling in NEMO-deficient cells, and interacted with TRAF6. Our results indicate that the IKKβ binding domain of NEMO possesses an ordered structure in the unbound state, provided that it is constrained within a dimer as is the case in the constitutively dimeric full-length NEMO protein. The stability of the NEMO coiled coil is maintained by strong interhelix interactions in the region centered on residue 54. The disulfide-linked constructs we describe herein may be useful for crystallization of NEMO's IKKβ binding domain in the absence of bound IKKβ, thereby facilitating the structural characterization of small-molecule inhibitors.

Detection of cyclobutane thymine dimers in DNA of human cells with monoclonal antibodies raised against a thymine dimer-containing tetranucleotide

Energy Technology Data Exchange (ETDEWEB)

Roza, L; Wulp, K.J.M. van der; MacFarlane, S J; Lohman, P H.M.; Baan, R A

1988-11-01

A hybrid cell line (hybridoma) has been isolated after fusion between mouse-plasmacytoma cells and spleen cells from mice immunized with a thymine dimer-containing tetranucleotide coupled to a carrier protein. Monoclonal antibodies produced by this hybridoma were characterized by testing the effect of various inhibitors in a competitive enzyme-linked immunosorbent assay (ELISA). The antibodies have a high specificity for thymine dimers in single-stranded DNA or poly(dT), but do not bind UV-irradiated d(TpC)/sub 5/. Less binding is observed with short thymine dimer-containing sequences. In vitro treatment of UV-irradiated DNA with photoreactivating enzyme in the presence of light, or with Micrococcus luteus UV-endonuclease results in disappearance of antigenicity. Antibody-binding to DNA isolated from UV-irradiated human fibroblasts (at 254 nm) is linear with dose. Removal of thymine dimers in these cells during a post-irradiation incubation, as detected with the antibodies, is fast initially but the rate rapidly decreases (about 50% residual dimers at 20 h after 10 J/m/sup 2/). The induction of thymine dimers in human skin irradiated with low doses of UV-B, too, was demonstrated immunochemically, by ELISA as well as by quantitative immunofluorescence microscopy.

Family C 7TM receptor dimerization and activation

DEFF Research Database (Denmark)

Bonde, Marie Mi; Sheikh, Søren P; Hansen, Jakob Lerche

2006-01-01

The family C seven transmembrane (7TM) receptors constitutes a small and especially well characterized subfamily of the large 7TM receptor superfamily. Approximately 50% of current prescription drugs target 7TM receptors, this biologically important family represents the largest class of drug...... to be fully defined. This review presents the biochemical support for family C 7TM receptor dimerization and discusses its importance for receptor biosynthesis, surface expression, ligand binding and activation, since lessons learnt here may well be applicable to the whole superfamily of 7TM receptors.......-targets today. It is well established that family C 7TM receptors form homo- or hetero-dimers on the cell surface of living cells. The large extra-cellular domains (ECD) have been crystallized as a dimer in the presence and absence of agonist. Upon agonist binding, the dimeric ECD undergoes large conformational...

Quantum-statistical mechanics of an atom-dimer mixture: Lee-Yang cluster expansion approach

International Nuclear Information System (INIS)

Ohkuma, Takahiro; Ueda, Masahito

2006-01-01

We use the Lee-Yang cluster expansion method to study quantum-statistical properties of a mixture of interconvertible atoms and dimers, where the dimers form in a two-body bound state of the atoms. We point out an infinite series of cluster diagrams whose summation leads to the Bose-Einstein condensation of the dimers below a critical temperature. Our theory captures some important features of a cold atom-dimer mixture such as interconversion of atoms and dimers and properties of the mixture at the unitarity limit

Liquid crystal dimers

CERN Document Server

Kumar Pal, Santanu

2017-01-01

This book covers in-depth discussion of design principles, synthesis and thermal behavior of all types of liquid crystal (LC) dimers. The text presents recent advances in the field of LC dimers consisting of different mesogenic units such as calamitic, discotic and bent-core molecules. It starts with a chapter on the introduction of liquid crystal dimers, including their odd-even behavior, basic classification of dimers and common mesophases in dimers. The text shows how the molecular architectures are being used to develop new materials to study a range of interesting phenomena such as the biaxial nematic phase containing rod-like and disc-like mesogenic units. Finally, the text presents perspectives related to technological relevance of these dimers such as dopants in LC display mixtures exhibiting faster relaxation time, strong flexoelectric coupling and others to effect control over the properties of these materials.

Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells

International Nuclear Information System (INIS)

Dietz, Marina S; Haße, Daniel; Ferraris, Davide M; Göhler, Antonia; Niemann, Hartmut H; Heilemann, Mike

2013-01-01

The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.

Synthesis and Diels–Alder cycloaddition reaction of norbornadiene and benzonorbornadiene dimers

Directory of Open Access Journals (Sweden)

Bilal Nişancı

2009-08-01

Full Text Available Dimeric forms of norbornadiene and benzonorbornadiene were synthesized starting with known monobromide derivatives. The Diels–Alder cycloaddition reaction of dimers with TCNE and PTAD was investigated and new norbornenoid polycyclics were obtained. All compounds were characterized properly using NMR spectroscopy.

Dimer and String Formation during Low Temperature Silicon Deposition on Si(100)

DEFF Research Database (Denmark)

Smith, A. P.; Jonsson, Hannes

1996-01-01

We present theoretical results based on density functional theory and kinetic Monte Carlo simulations of silicon deposition and address observations made in recently reported low temperature scanning tunneling microscopy studies. A mechanism is presented which explains dimer formation on top...... of the substrate's dimer rows at 160 K and up to room temperature, while between-row dimers and longer strings of adatoms (''diluted dimer rows'') form at higher temperature. A crossover occurs at around room temperature between two different mechanisms for adatom diffusion in our model....

Dimerization of a flocculent protein from Moringa oleifera: experimental evidence and in silico interpretation.

Science.gov (United States)

Pavankumar, Asalapuram R; Kayathri, Rajarathinam; Murugan, Natarajan A; Zhang, Qiong; Srivastava, Vaibhav; Okoli, Chuka; Bulone, Vincent; Rajarao, Gunaratna K; Ågren, Hans

2014-01-01

Many proteins exist in dimeric and other oligomeric forms to gain stability and functional advantages. In this study, the dimerization property of a coagulant protein (MO2.1) from Moringa oleifera seeds was addressed through laboratory experiments, protein-protein docking studies and binding free energy calculations. The structure of MO2.1 was predicted by homology modelling, while binding free energy and residues-distance profile analyses provided insight into the energetics and structural factors for dimer formation. Since the coagulation activities of the monomeric and dimeric forms of MO2.1 were comparable, it was concluded that oligomerization does not affect the biological activity of the protein.

Dynamics of the water dimer + nitric oxide collision

Energy Technology Data Exchange (ETDEWEB)

Ree, Jong Baik [Dept. of Chemistry Education, Chonnam National University, Gwangju (Korea, Republic of); Kim, Yoo Hang [Dept. of Chemistry, Inha University, Incheon (Korea, Republic of); Shin, Hyung Kyu [Dept. of Chemistry, University of Nevada, Nevada (Korea, Republic of)

2017-02-15

Collision-induced intermolecular energy transfer and intramolecular vibrational redistribution in the collision of a water dimer and nitric oxide are studied by use of quasiclassical procedures. Intermolecular energy flow is shown to occur mainly through a direct-mode mechanism transferring relatively large amounts in strong collisions. About a quarter of the energy initially deposited in the dimer transfers to the ground state NO, while the rest redistributes among internal motions of the collision system. The main portion of initial energy deposited in the dimer redistributes in the stretches of the donor monomer through the 1:1 resonance followed by in the bend through the 1:2 resonance. Energy transfer from the excited NO to the ground-state dimer is equally efficient, transferring more than half the initial excitation to the donor monomer, the efficiency that is attributed to the internal modes operating as energy reservoirs. The hydrogen bond shares about 15% of the initial excitation stored in both dimer-to-NO and NO-to-dimer processes as a result of strong coupling of the hydrogen bond with the proton-donor OH bond of the monomer. A small fraction of collisions proceeds through a complex-mode mechanism and lead to NO dissociation, the dissociated O atom showing a propensity to form a new hydrogen bond.

cis elements and trans-acting factors involved in dimer formation of murine leukemia virus RNA.

Science.gov (United States)

Prats, A C; Roy, C; Wang, P A; Erard, M; Housset, V; Gabus, C; Paoletti, C; Darlix, J L

1990-02-01

The genetic material of all retroviruses examined so far consists of two identical RNA molecules joined at their 5' ends by the dimer linkage structure (DLS). Since the precise location of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analyzed the dimerization process of Moloney murine leukemia virus (MoMuLV) genomic RNA. For this purpose we derived an in vitro model for RNA dimerization. By using this model, murine leukemia virus RNA was shown to form dimeric molecules. Deletion mutagenesis in the 620-nucleotide leader of MoMuLV RNA showed that the dimer promoting sequences are located within the encapsidation element Psi between positions 215 and 420. Furthermore, hybridization assays in which DNA oligomers were used to probe monomer and dimer forms of MoMuLV RNA indicated that the DLS probably maps between positions 280 and 330 from the RNA 5' end. Also, retroviral nucleocapsid protein was shown to catalyze dimerization of MoMuLV RNA and to be tightly bound to genomic dimer RNA in virions. These results suggest that MoMuLV RNA dimerization and encapsidation are probably controlled by the same cis element, Psi, and trans-acting factor, nucleocapsid protein, and thus might be linked during virion formation.

Adsorption of dimeric surfactants in lamellar silicates

Energy Technology Data Exchange (ETDEWEB)

Balcerzak, Mateusz; Pietralik, Zuzanna [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland); Domka, Ludwik [Department of Metalorganic Chemistry, Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznań (Poland); Skrzypczak, Andrzej [Institute of Chemical Technology, Poznań University of Technology, Berdychowo 4, 60-965 Poznań (Poland); Kozak, Maciej, E-mail: mkozak@amu.edu.pl [Department of Macromolecular Physics, Faculty of Physics, A. Mickiewicz University, Umultowska 85, 61-614 Poznań (Poland)

2015-12-01

Highlights: • The intercalation of dimeric surfactants changed the morphology of MMT samples. • XRD indicated structures formed by surfactant molecules in interlayer space. • The four-step thermal decomposition of dimeric surfactant, confirms intercalation. - Abstract: The adsorption of different types of cationic surfactants in lamellar silicates changes their surface character from hydrophilic to hydrophobic. This study was undertaken to obtain lamellar silicates modified by a series of novel dimeric (gemini) surfactants of different length alkyl chains and to characterise these organophilised materials. Synthetic sodium montmorillonite SOMASIF® ME 100 (M) and enriched bentonite of natural origin (Nanoclay – hydrophilic bentonite®) were organophilised with dimeric (gemini) surfactants (1,1′-(1,4-butanediyl)bis(alkoxymethyl)imidazolium dichlorides). As a result of surfactant molecule adsorption in interlamellar space, the d-spacing (d{sub 001}) increased from 0.97 nm (for the anhydrous structure) to 2.04 nm. A Fourier transform infrared spectroscopy (FTIR) analysis of the modified systems reveals bands assigned to the stretching vibrations of the CH{sub 2} and CH{sub 3} groups and the scissoring vibrations of the NH group from the structure of the dimeric surfactants. Thermogravimetric (TG) and derivative thermogravimetric (DTG) studies imply a four-stage process of surfactant decomposition. Scanning electron microscopy (SEM) images provide information on the influence of dimeric surfactant intercalation into the silicate structures. Particles of the modified systems show a tendency toward the formation of irregularly shaped agglomerates.

Data on dimer formation between importin α subtypes

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Yoichi Miyamoto

2016-06-01

Full Text Available This article describes data related to the research article titled “Functional characterization of importin α8 as a classical nuclear localization signal receptor” [1]. A GST pull-down assay showed that both importin α1 and α8, which are classical nuclear localization signal (cNLS receptors, can form a dimer with importin α6, α7, or α8. Importin α8 has higher dimer-forming ability than importin α1. In addition, our data show that either importin α1 or importin α8 can form a heterodimer with importin α3, which exists in a preformed complex with cNLS substrates such as the conventional SV40TNLS or the p53 protein, resulting in the release of the cNLS substrates from importin α3.

Dimerization of 3He in 3He-4He mixture films

International Nuclear Information System (INIS)

Bashkin, E.

1994-01-01

3 He atoms dissolved in superfluid 4 He may form dimers ( 3 He) 2 in two-dimensional geometries. Dimer formation is studied in films of dilute 3 He- 4 He mixture. After designing a schematic 3 He- 3 He interaction potential, the dimer binding energy is calculated for various substrates. It is shown that 3 He impurity states localized near the substrate give rise to the highest magnitudes of the binding energy. (author). 32 refs., 6 figs.,; 1 tab

Covalent α-synuclein dimers: chemico-physical and aggregation properties.

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Micaela Pivato

Full Text Available The aggregation of α-synuclein into amyloid fibrils constitutes a key step in the onset of Parkinson's disease. Amyloid fibrils of α-synuclein are the major component of Lewy bodies, histological hallmarks of the disease. Little is known about the mechanism of aggregation of α-synuclein. During this process, α-synuclein forms transient intermediates that are considered to be toxic species. The dimerization of α-synuclein could represent a rate-limiting step in the aggregation of the protein. Here, we analyzed four covalent dimers of α-synuclein, obtained by covalent link of the N-terms, C-terms, tandem cloning of two sequences and tandem juxtaposition in one protein of the 1-104 and 29-140 sequences. Their biophysical properties in solution were determined by CD, FT-IR and NMR spectroscopies. SDS-induced folding was also studied. The fibrils formation was analyzed by ThT and polarization fluorescence assays. Their morphology was investigated by TEM and AFM-based quantitative morphometric analysis. All dimers were found to be devoid of ordered secondary structure under physiological conditions and undergo α-helical transition upon interaction with SDS. All protein species are able to form amyloid-like fibrils. The reciprocal orientation of the α-synuclein monomers in the dimeric constructs affects the kinetics of the aggregation process and a scale of relative amyloidogenic propensity was determined. Structural investigations by FT IR spectroscopy, and proteolytic mapping of the fibril core did not evidence remarkable difference among the species, whereas morphological analyses showed that fibrils formed by dimers display a lower and diversified level of organization in comparison with α-synuclein fibrils. This study demonstrates that although α-synuclein dimerization does not imply the acquisition of a preferred conformation by the participating monomers, it can strongly affect the aggregation properties of the molecules. The results

Dimerization of nitrophorin 4 at low pH and comparison to the K1A mutant of nitrophorin 1.

Science.gov (United States)

Berry, Robert E; Yang, Fei; Shokhireva, Tatiana K; Amoia, Angela M; Garrett, Sarah A; Goren, Allena M; Korte, Stephanie R; Zhang, Hongjun; Weichsel, Andrzej; Montfort, William R; Walker, F Ann

2015-01-20

Nitrophorin 4, one of the four NO-carrying heme proteins from the salivary glands of Rhodnius prolixus, forms a homodimer at pH 5.0 with a Kd of ∼8 μM. This dimer begins to dissociate at pH 5.5 and is completely dissociated to monomer at pH 7.3, even at 3.7 mM. The dimer is significantly stabilized by binding NO to the heme and at pH 7.3 would require dilution to well below 0.2 mM to completely dissociate the NP4-NO homodimer. The primary techniques used for investigating the homodimer and the monomer-dimer equilibrium were size-exclusion fast protein liquid chromatography at pH 5.0 and (1)H{(15)N} heteronuclear single-quantum coherence spectroscopy as a function of pH and concentration. Preparation of site-directed mutants of NP4 (A1K, D30A, D30N, V36A/D129A/L130A, K38A, R39A, K125A, K125E, D132A, L133V, and K38Q/R39Q/K125Q) showed that the N-terminus, D30, D129, D132, at least one heme propionate, and, by association, likely also E32 and D35 are involved in the dimerization. The "closed loop" form of the A-B and G-H flexible loops of monomeric NP4, which predominates in crystal structures of the monomeric protein reported at pH 5.6 but not at pH 7.5 and which involves all of the residues listed above except D132, is required for dimer formation. Wild-type NP1 does not form a homodimer, but NP1(K1A) and native N-terminal NP1 form dimers in the presence of NO. The homodimer of NP1, however, is considerably less stable than that of NP4 in the absence of NO. This suggests that additional aspartate or glutamate residues present in the C-terminal region of NP4, but not NP1, are also involved in stabilizing the dimer.

Laser isotope separation using selective inhibition and encouragement of dimer formation

International Nuclear Information System (INIS)

Kivel, B.

1979-01-01

Method and apparatus for inhibiting dimer formation of molecules of a selected isotope type in a cooled flow of gas to enhance the effectiveness of mass difference isotope separation techniques are described. Molecules in the flow containing atoms of the selected isotope type are selectively excited by infrared radiation in order to inhibit the formation of dimers and larger clusters of such molecules, while the molecules not containing atoms of the selected, excited type are encouraged to form dimers and higher order aggregates by the cooling of the gaseous flow. The molecules with the excited isotope will predominate in monomers and will constitute the enriched product stream, while the aggregated group comprising molecules having the unexcited isotope will predominate in dimers and larger clusters of molecules, forming the tails stream. The difference in diffusion coefficientts between particles of the excited and unexcited isotopes is enhanced by the greater mass differences resulting from aggregation of unexcited particles into dimers and larger clusters. Prior art separation techniques which exploit differences in isotopic diffusion rates will consequently exhibit enhanced enrichment per stage by the utilization of the present invention

SH2B1 regulation of energy balance, body weight, and glucose metabolism

OpenAIRE

Rui, Liangyou

2014-01-01

The Src homology 2B (SH2B) family members (SH2B1, SH2B2 and SH2B3) are adaptor signaling proteins containing characteristic SH2 and PH domains. SH2B1 (also called SH2-B and PSM) and SH2B2 (also called APS) are able to form homo- or hetero-dimers via their N-terminal dimerization domains. Their C-terminal SH2 domains bind to tyrosyl phosphorylated proteins, including Janus kinase 2 (JAK2), TrkA, insulin receptors, insulin-like growth factor-1 receptors, insulin receptor substrate-1 (IRS1), and...

Analytical expressions for the correlation function of a hard sphere dimer fluid

Science.gov (United States)

Kim, Soonho; Chang, Jaeeon; Kim, Hwayong

A closed form expression is given for the correlation function of a hard sphere dimer fluid. A set of integral equations is obtained from Wertheim's multidensity Ornstein-Zernike integral equation theory with Percus-Yevick approximation. Applying the Laplace transformation method to the integral equations and then solving the resulting equations algebraically, the Laplace transforms of the individual correlation functions are obtained. By the inverse Laplace transformation, the radial distribution function (RDF) is obtained in closed form out to 3D (D is the segment diameter). The analytical expression for the RDF of the hard dimer should be useful in developing the perturbation theory of dimer fluids.

21 CFR 176.120 - Alkyl ketene dimers.

Science.gov (United States)

2010-04-01

..., processing, preparing, treating, packaging, transporting, or holding food, subject to the provisions of this... paperboard. (c) The alkyl ketene dimers may be used in the form of an aqueous emulsion which may contain...

Radiation-induced tetramer-to-dimer transition of Escherichia coli lactose repressor

International Nuclear Information System (INIS)

Goffinont, S.; Davidkova, M.; Spotheim-Maurizot, M.

2009-01-01

The wild type lactose repressor of Escherichia coli is a tetrameric protein formed by two identical dimers. They are associated via a C-terminal 4-helix bundle (called tetramerization domain) whose stability is ensured by the interaction of leucine zipper motifs. Upon in vitro γ-irradiation the repressor losses its ability to bind the operator DNA sequence due to damage of its DNA-binding domains. Using an engineered dimeric repressor for comparison, we show here that irradiation induces also the change of repressor oligomerisation state from tetramer to dimer. The splitting of the tetramer into dimers can result from the oxidation of the leucine residues of the tetramerization domain.

Dimerization of the Glucan Phosphatase Laforin Requires the Participation of Cysteine 329

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Sánchez-Martín, Pablo; Raththagala, Madushi; Bridges, Travis M.; Husodo, Satrio; Gentry, Matthew S.; Sanz, Pascual; Romá-Mateo, Carlos

2013-01-01

Laforin, encoded by a gene that is mutated in Lafora Disease (LD, OMIM 254780), is a modular protein composed of a carbohydrate-binding module and a dual-specificity phosphatase domain. Laforin is the founding member of the glucan-phosphatase family and regulates the levels of phosphate present in glycogen. Multiple reports have described the capability of laforin to form dimers, although the function of these dimers and their relationship with LD remains unclear. Recent evidence suggests that laforin dimerization depends on redox conditions, suggesting that disulfide bonds are involved in laforin dimerization. Using site-directed mutagenesis we constructed laforin mutants in which individual cysteine residues were replaced by serine and then tested the ability of each protein to dimerize using recombinant protein as well as a mammalian cell culture assay. Laforin-Cys329Ser was the only Cys/Ser mutant unable to form dimers in both assays. We also generated a laforin truncation lacking the last three amino acids, laforin-Cys329X, and this truncation also failed to dimerize. Interestingly, laforin-Cys329Ser and laforin-Cys329X were able to bind glucans, and maintained wild type phosphatase activity against both exogenous and biologically relevant substrates. Furthermore, laforin-Cys329Ser was fully capable of participating in the ubiquitination process driven by a laforin-malin complex. These results suggest that dimerization is not required for laforin phosphatase activity, glucan binding, or for the formation of a functional laforin-malin complex. Cumulatively, these results suggest that cysteine 329 is specifically involved in the dimerization process of laforin. Therefore, the C329S mutant constitutes a valuable tool to analyze the physiological implications of laforin’s oligomerization. PMID:23922729

Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation.

Science.gov (United States)

Corrada, Dario; Soshilov, Anatoly A; Denison, Michael S; Bonati, Laura

2016-06-01

The Aryl hydrocarbon Receptor (AhR) is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT) protein, occurring through the Helix-Loop-Helix (HLH) and PER-ARNT-SIM (PAS) domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms underlying the

Deciphering Dimerization Modes of PAS Domains: Computational and Experimental Analyses of the AhR:ARNT Complex Reveal New Insights Into the Mechanisms of AhR Transformation.

Directory of Open Access Journals (Sweden)

Dario Corrada

2016-06-01

Full Text Available The Aryl hydrocarbon Receptor (AhR is a transcription factor that mediates the biochemical response to xenobiotics and the toxic effects of a number of environmental contaminants, including dioxins. Recently, endogenous regulatory roles for the AhR in normal physiology and development have also been reported, thus extending the interest in understanding its molecular mechanisms of activation. Since dimerization with the AhR Nuclear Translocator (ARNT protein, occurring through the Helix-Loop-Helix (HLH and PER-ARNT-SIM (PAS domains, is needed to convert the AhR into its transcriptionally active form, deciphering the AhR:ARNT dimerization mode would provide insights into the mechanisms of AhR transformation. Here we present homology models of the murine AhR:ARNT PAS domain dimer developed using recently available X-ray structures of other bHLH-PAS protein dimers. Due to the different reciprocal orientation and interaction surfaces in the different template dimers, two alternative models were developed for both the PAS-A and PAS-B dimers and they were characterized by combining a number of computational evaluations. Both well-established hot spot prediction methods and new approaches to analyze individual residue and residue-pairwise contributions to the MM-GBSA binding free energies were adopted to predict residues critical for dimer stabilization. On this basis, a mutagenesis strategy for both the murine AhR and ARNT proteins was designed and ligand-dependent DNA binding ability of the AhR:ARNT heterodimer mutants was evaluated. While functional analysis disfavored the HIF2α:ARNT heterodimer-based PAS-B model, most mutants derived from the CLOCK:BMAL1-based AhR:ARNT dimer models of both the PAS-A and the PAS-B dramatically decreased the levels of DNA binding, suggesting this latter model as the most suitable for describing AhR:ARNT dimerization. These novel results open new research directions focused at elucidating basic molecular mechanisms

Neutral dipole-dipole dimers: A new field in science

Science.gov (United States)

Kosower, Edward M.; Borz, Galina

2018-03-01

Dimer formation with dipole neutralization produces species such as low polarity water (LPW) compatible with hydrophobic surfaces (Phys. Chem. Chem. Phys. 2015, 17, 24895-24900) Dimerization and dipole neutralization occurs for N-methylacetamide on polyethylene, a behavior drastically different from its contortions in acetonitrile on AgBr:AgCl planar crystals (AgX) (ChemPhysChem 2014, 15, 3598-3607). The weak infrared absorption of the amide dimer on polyethylene is shown experimentally. Dimerization of palmitic acid is shown along with some of the many ramifications for intracellular systems. Polyoligomers of water are present on polyethylene surfaces. Some high resolution spectra of three of the polyoligomers of water are shown along with a mechanistic scheme for polyoligomer formation and dissolution. The structures of some of the oligomers are known from spectroscopic studies of water on AgX. The scope of the article begins with PE, generally accepted as hydrophobic. The IR of PE revealed not only that water was present but that it appeared in two forms, oligomers (O) and polyoligomers (PO). How did we recognize what they were? These species had been observed as especially strong "marker" peaks in the spectra1 of water placed on planar AgX, a platform developed by Katzir and his coworkers [6]. But there was a problem: the proximity to PE of oligomers with substantial (calculated) dipole moments and thus polarity, including cyclic hexamers of water (chair and boat forms), the cyclic pentamer, the books I and II, and the cyclic trimer [7a]. Another link was needed, a role perfectly fit by the already cited low polarity water (LPW). The choice was experimentally supported by the detection of low intensity absorption in the bending region.Some important generalities flow from these results. What other dimers might be present in the biological or chemical world? Palmitic acid dimer (PAD) would be a candidate for decreasing the polarity of the acid (PA). Another

Comparison of FDTD numerical computations and analytical multipole expansion method for plasmonics-active nanosphere dimers.

Science.gov (United States)

Dhawan, Anuj; Norton, Stephen J; Gerhold, Michael D; Vo-Dinh, Tuan

2009-06-08

This paper describes a comparative study of finite-difference time-domain (FDTD) and analytical evaluations of electromagnetic fields in the vicinity of dimers of metallic nanospheres of plasmonics-active metals. The results of these two computational methods, to determine electromagnetic field enhancement in the region often referred to as "hot spots" between the two nanospheres forming the dimer, were compared and a strong correlation observed for gold dimers. The analytical evaluation involved the use of the spherical-harmonic addition theorem to relate the multipole expansion coefficients between the two nanospheres. In these evaluations, the spacing between two nanospheres forming the dimer was varied to obtain the effect of nanoparticle spacing on the electromagnetic fields in the regions between the nanostructures. Gold and silver were the metals investigated in our work as they exhibit substantial plasmon resonance properties in the ultraviolet, visible, and near-infrared spectral regimes. The results indicate excellent correlation between the two computational methods, especially for gold nanosphere dimers with only a 5-10% difference between the two methods. The effect of varying the diameters of the nanospheres forming the dimer, on the electromagnetic field enhancement, was also studied.

The two-state dimer receptor model: a general model for receptor dimers.

Science.gov (United States)

Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferrada, Carla; Ferré, Sergi; Fuxe, Kjell; Cortés, Antoni; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

2006-06-01

Nonlinear Scatchard plots are often found for agonist binding to G-protein-coupled receptors. Because there is clear evidence of receptor dimerization, these nonlinear Scatchard plots can reflect cooperativity on agonist binding to the two binding sites in the dimer. According to this, the "two-state dimer receptor model" has been recently derived. In this article, the performance of the model has been analyzed in fitting data of agonist binding to A(1) adenosine receptors, which are an example of receptor displaying concave downward Scatchard plots. Analysis of agonist/antagonist competition data for dopamine D(1) receptors using the two-state dimer receptor model has also been performed. Although fitting to the two-state dimer receptor model was similar to the fitting to the "two-independent-site receptor model", the former is simpler, and a discrimination test selects the two-state dimer receptor model as the best. This model was also very robust in fitting data of estrogen binding to the estrogen receptor, for which Scatchard plots are concave upward. On the one hand, the model would predict the already demonstrated existence of estrogen receptor dimers. On the other hand, the model would predict that concave upward Scatchard plots reflect positive cooperativity, which can be neither predicted nor explained by assuming the existence of two different affinity states. In summary, the two-state dimer receptor model is good for fitting data of binding to dimeric receptors displaying either linear, concave upward, or concave downward Scatchard plots.

In Situ Structural Characterization of Ferric Iron Dimers in Aqueous Solutions

DEFF Research Database (Denmark)

Zhu, Mengqiang; Puls, Brendan W.; Frandsen, Cathrine

2013-01-01

The structure of ferric iron (Fe3+) dimers in aqueous solutions has long been debated. In this work, we have determined the dimer structure in situ in aqueous solutions using extended X-ray absorption fine structure (EXAFS) spectroscopy. An Fe K-edge EXAFS analysis of 0.2 M ferric nitrate solutions...... at pH 1.28–1.81 identified a Fe–Fe distance at ∼3.6 Å, strongly indicating that the dimers take the μ-oxo form. The EXAFS analysis also indicates two short Fe–O bonds at ∼1.80 Å and ten long Fe–O bonds at ∼2.08 Å, consistent with the μ-oxo dimer structure. The scattering from the Fe–Fe paths interferes...... confirmed by Mössbauer analyses of analogous quick frozen solutions. This work also explores the electronic structure and the relative stability of the μ-oxo dimer in a comparison to the dihydroxo dimer using density function theory (DFT) calculations. The identification of such dimers in aqueous solutions...

Morphological and physiological retinal degeneration induced by intravenous delivery of vitamin A dimers in rabbits

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Jackie Penn

2015-02-01

Full Text Available The eye uses vitamin A as a cofactor to sense light and, during this process, some vitamin A molecules dimerize, forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD and Stargardt disease is the accumulation of these dimers in the retinal pigment epithelium (RPE and Bruch’s membrane (BM. However, it is not known whether dimers of vitamin A are secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography-free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E-damaged photoreceptors and RPE cells triggered inflammation, induced remolding of the choroidal vasculature and triggered a decline in the retina’s response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.

Her4 and Her2/neu tyrosine kinase domains dimerize and activate in a reconstituted in vitro system.

Science.gov (United States)

Monsey, John; Shen, Wei; Schlesinger, Paul; Bose, Ron

2010-03-05

Her4 (ErbB-4) and Her2/neu (ErbB-2) are receptor-tyrosine kinases belonging to the epidermal growth factor receptor (EGFR) family. Crystal structures of EGFR and Her4 kinase domains demonstrate kinase dimerization and activation through an allosteric mechanism. The kinase domains form an asymmetric dimer, where the C-lobe surface of one monomer contacts the N-lobe of the other monomer. EGFR kinase dimerization and activation in vitro was previously reported using a nickel-chelating lipid-liposome system, and we now apply this system to all other members of the EGFR family. Polyhistidine-tagged Her4, Her2/neu, and Her3 kinase domains are bound to these nickel-liposomes and are brought to high local concentration, mimicking what happens to full-length receptors in vivo following ligand binding. Addition of nickel-liposomes to Her4 kinase domain results in 40-fold activation in kinase activity and marked enhancement of C-terminal tail autophosphorylation. Activation of Her4 shows a sigmoidal dependence on kinase concentration, consistent with a cooperative process requiring kinase dimerization. Her2/neu kinase activity is also activated by nickel-liposomes, and is increased further by heterodimerization with Her3 or Her4. The ability of Her3 and Her4 to heterodimerize and activate other family members is studied in vitro. Her3 kinase domain readily activates Her2/neu but is a poor activator of Her4, which differs from the prediction made by the asymmetric dimer model. Mutation of Her3 residues (952)ENI(954) to the corresponding sequence in Her4 enhanced the ability of Her3 to activate Her4, demonstrating that sequence differences on the C-lobe surface influence the heterodimerization and activation of ErbB kinase domains.

A short autocomplementary sequence plays an essential role in avian sarcoma-leukosis virus RNA dimerization.

Science.gov (United States)

Fossé, P; Motté, N; Roumier, A; Gabus, C; Muriaux, D; Darlix, J L; Paoletti, J

1996-12-24

Retroviral genomes consist of two identical RNA molecules joined noncovalently near their 5'-ends. Recently, two models have been proposed for RNA dimer formation on the basis of results obtained in vitro with human immunodeficiency virus type 1 RNA and Moloney murine leukemia virus RNA. It was first proposed that viral RNA dimerizes by forming an interstrand quadruple helix with purine tetrads. The second model postulates that RNA dimerization is initiated by a loop-loop interaction between the two RNA molecules. In order to better characterize the dimerization process of retroviral genomic RNA, we analyzed the in vitro dimerization of avian sarcoma-leukosis virus (ASLV) RNA using different transcripts. We determined the requirements for heterodimer formation, the thermal dissociation of RNA dimers, and the influence of antisense DNA oligonucleotides on dimer formation. Our results strongly suggest that purine tetrads are not involved in dimer formation. Data show that an autocomplementary sequence located upstream from the splice donor site and within a major packaging signal plays a crucial role in ASLV RNA dimer formation in vitro. This sequence is able to form a stem-loop structure, and phylogenetic analysis reveals that it is conserved in 28 different avian sarcoma and leukosis viruses. These results suggest that dimerization of ASLV RNA is initiated by a loop-loop interaction between two RNA molecules and provide an additional argument for the ubiquity of the dimerization process via loop-loop interaction.

Cyclobutyl pyrimidine dimer accumulation in relation to UV-B sensitivity in mung bean cultivars

International Nuclear Information System (INIS)

He Junmin; Wang Ruibin; Meng Zhaoni

2006-01-01

The purpose of the experiment is to reveal the relationship between cyclobutyl pyrimidine dimers (CPDs) accumulation and UV-B sensitivity in mung bean cultivars. Two mung bean cultivars (Phaseolus raditus L. cv. Qindou -2 0 and Zhonglü -1 ) were grown in greenhouse with treatment or without treatment of UV-B radiation (0.4 W * m -2 ) for four days. The UV-B-induced CPDs in mung bean DNA were quantified by enzyme-linked immunosorbent assay (ELISA) with specific monoclonal antibody and the relationship between CPDs accumulation and the UV-B sensitivity of mung bean seedlings were discussed. The UV-B-induced inhibition of the biomass and net photosynthetic rate of the primary leaves of cultivar Zhonglü -1 were respectively lower than that of cultivar Qindou -2 0, so that the cultivar Zhonglü -1 was more tolerant to UV-B than the cultivar Qindou -2 0. Meanwhile, the cultivar Zhonglü -1 had lower CPD accumulation and susceptibility to CPD induction, higher photorepair capacity and same dark repair capacity as compared with the cultivar Qindou -2 0. Different UV-B sensitivities between two mung bean cultivars may be mainly caused by the differences in CPD accumulation, which are caused by the different susceptibility to CPD induction and the different photorepair capacities. In addition, the different susceptibility to CPD induction between two mung bean cultivars is related to the different levels of UV-absorbing compounds

Modulation of BCR Signaling by the Induced Dimerization of Receptor-Associated SYK

Directory of Open Access Journals (Sweden)

Mark L. Westbroek

2017-12-01

Full Text Available Clustering of the B cell antigen receptor (BCR by polyvalent antigens is transmitted through the SYK tyrosine kinase to the activation of multiple intracellular pathways that determine the physiological consequences of receptor engagement. To explore factors that modulate the quantity and quality of signals sent by the crosslinked BCR, we developed a novel chemical mediator of dimerization to induce clustering of receptor-associated SYK. To accomplish this, we fused SYK with E. coli dihydrofolate reductase (eDHFR, which binds the small molecule trimethoprim (TMP with high affinity and selectivity and synthesized a dimer of TMP with a flexible linker. The TMP dimer is able to induce the aggregation of eDHFR-linked SYK in live cells. The induced dimerization of SYK bound to the BCR differentially regulates the activation of downstream transcription factors, promoting the activation of Nuclear Factor of Activated T cells (NFAT without affecting the activation of NFκB. The dimerization of SYK enhances the duration but not the amplitude of calcium mobilization by enhancing the extent and duration of its interaction with the crosslinked BCR at the plasma membrane.

Elucidation of the Specific Formation of Homo- and Heterodimeric Forms of ThbZIP1 and Its Role in Stress

Directory of Open Access Journals (Sweden)

Xianguang Nie

2014-06-01

Full Text Available Protein–protein interactions are important for the molecular understanding of the biological processes of proteins. The dimerization of bZIPs (basic leucine zipper proteins is involved in modifying binding site specificities, altering dimer stability, and permitting a new set of specific protein-to-protein interactions to occur at the promoter. In the present study, we studied the whether ThbZIP1 form homo- and heterodimers using the yeast two-hybrid method. Five bZIP genes were cloned from Tamarix hispida to investigate their interaction with ThbZIP1. Our results showed that ThbZIP1 can form homodimers with itself, and three out of five bZIPs could interact with the ThbZIP1 protein to form heterodimers. Real-time RT-PCR results suggested that these ThbZIPs can all respond to abiotic stresses and abscisic acid (ABA, and shared very similar expression patterns in response to NaCl, ABA or PEG6000. Subcellular localization studies showed that all ThbZIPs are targeted to the nucleus. Our results showed that ThbZIP1 are dimeric proteins, which can form homo- or heterodimers.

Cyclic Hexapeptide Dimers, Antatollamides A and B, from the Ascidian Didemnum molle. A Tryptophan-Derived Auxiliary for l- and d-Amino Acid Assignments.

Science.gov (United States)

Salib, Mariam N; Molinski, Tadeusz F

2017-10-06

Two dimerized cyclic hexapeptides, antatollamides A (1) and B (2), were isolated from the colonial ascidian Didemnum molle collected in Pohnpei. The amino acid compositions and sequences were determined by interpretation of MS and 1D and 2D NMR data. Raney Ni reduction of antatollamide A cleaved the dimer to the corresponding monomeric cyclic hexapeptide with replacement of Cys by Ala. The amino acid configuration of 1 was established, after total hydrolysis, by derivatization with a new chiral reagent, (5-fluoro-2,4-dinitrophenyl)-N α -l-tryptophanamide (FDTA), prepared from l-Trp, followed by LCMS analysis; all amino acids were found to be l-configured except for d-Ala.

Study of DNA Origami Dimerization and Dimer Dissociation Dynamics and of the Factors that Limit Dimerization.

Science.gov (United States)

Liber, Miran; Tomov, Toma E; Tsukanov, Roman; Berger, Yaron; Popov, Mary; Khara, Dinesh C; Nir, Eyal

2018-06-01

Organizing DNA origami building blocks into higher order structures is essential for fabrication of large structurally and functionally diverse devices and molecular machines. Unfortunately, the yields of origami building block attachment reactions are typically not sufficient to allow programed assembly of DNA devices made from more than a few origami building blocks. To investigate possible reasons for these low yields, a detailed single-molecule fluorescence study of the dynamics of rectangular origami dimerization and origami dimer dissociation reactions is conducted. Reactions kinetics and yields are investigated at different origami and ion concentrations, for different ion types, for different lengths of bridging strands, and for the "sticky end" and "weaving welding" attachment techniques. Dimerization yields are never higher than 86%, which is typical for such systems. Analysis of the dynamic data shows that the low yield cannot be explained by thermodynamic instability or structural imperfections of the origami constructs. Atomic force microscopy and gel electrophoresis evidence reveal self-dimerization of the origami monomers, likely via blunt-end interactions made possible by the presence of bridging strands. It is suggested that this mechanism is the major factor that inhibits correct dimerization and means to overcome it are discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The structure of apo and holo forms of xylose reductase, a dimeric aldo-keto reductase from Candida tenuis.

Science.gov (United States)

Kavanagh, Kathryn L; Klimacek, Mario; Nidetzky, Bernd; Wilson, David K

2002-07-16

Xylose reductase is a homodimeric oxidoreductase dependent on NADPH or NADH and belongs to the largely monomeric aldo-keto reductase superfamily of proteins. It catalyzes the first step in the assimilation of xylose, an aldose found to be a major constituent monosaccharide of renewable plant hemicellulosic material, into yeast metabolic pathways. It does this by reducing open chain xylose to xylitol, which is reoxidized to xylulose by xylitol dehydrogenase and metabolically integrated via the pentose phosphate pathway. No structure has yet been determined for a xylose reductase, a dimeric aldo-keto reductase or a family 2 aldo-keto reductase. The structures of the Candida tenuis xylose reductase apo- and holoenzyme, which crystallize in spacegroup C2 with different unit cells, have been determined to 2.2 A resolution and an R-factor of 17.9 and 20.8%, respectively. Residues responsible for mediating the novel dimeric interface include Asp-178, Arg-181, Lys-202, Phe-206, Trp-313, and Pro-319. Alignments with other superfamily members indicate that these interactions are conserved in other dimeric xylose reductases but not throughout the remainder of the oligomeric aldo-keto reductases, predicting alternate modes of oligomerization for other families. An arrangement of side chains in a catalytic triad shows that Tyr-52 has a conserved function as a general acid. The loop that folds over the NAD(P)H cosubstrate is disordered in the apo form but becomes ordered upon cosubstrate binding. A slow conformational isomerization of this loop probably accounts for the observed rate-limiting step involving release of cosubstrate. Xylose binding (K(m) = 87 mM) is mediated by interactions with a binding pocket that is more polar than a typical aldo-keto reductase. Modeling of xylose into the active site of the holoenzyme using ordered waters as a guide for sugar hydroxyls suggests a convincing mode of substrate binding.

Molecular structure investigation of neutral, dimer and anion forms of 3,4-pyridinedicarboxylic acid: a combined experimental and theoretical study.

Science.gov (United States)

Karabacak, Mehmet; Bilgili, Sibel; Atac, Ahmet

2015-01-25

In this study, the structural and vibrational analysis of 3,4-pyridinedicarboxylic acid (3,4-PDCA) are presented using experimental techniques as FT-IR, FT-Raman, NMR, UV and quantum chemical calculations. FT-IR and FT-Raman spectra of 3,4-pyridinedicarboxylic acid in the solid phase are recorded in the region 4000-400 cm(-1) and 4000-50 cm(-1), respectively. The geometrical parameters and energies of all different and possible monomer, dimer, anion(-1) and anion(-2) conformers of 3,4-PDCA are obtained from Density Functional Theory (DFT) with B3LYP/6-311++G(d,p) basis set. There are sixteen conformers (C1C16) for this molecule (neutral form). The most stable conformer of 3,4-PDCA is the C1 conformer. The complete assignments are performed on the basis of the total energy distribution (TED) of the vibrational modes calculated with scaled quantum mechanics (SQM) method. (1)H and (13)C NMR spectra are recorded and the chemical shifts are calculated by using DFT/B3LYP methods with 6-311++G(d,p) basis set. The UV absorption spectrum of the studied compound is recorded in the range of 200-400 nm by dissolved in ethanol. The optimized geometric parameters were compared with experimental data via the X-ray results derived from complexes of this molecule. In addition these, molecular electrostatic potential (MEP), thermodynamic and electronic properties, HOMO-LUMO energies and Mulliken atomic charges, are performed. Copyright © 2014 Elsevier B.V. All rights reserved.

Mutability of bacteriophage M13 by ultraviolet light: role of pyrimidine dimers

International Nuclear Information System (INIS)

Schaaper, R.M.; Glickman, B.W.

1982-01-01

The role of pyrimidine dimers in mutagenesis by ultraviolet light was examined by measuring the UV-induced reversion of six different bacteriophage M13 amber mutants for which the neighboring DNA sequences are known. The mutational response at amber (TAG) codons preceded by a guanine or adenine (where no pyrimidine dimer can be formed) were compared with those preceded by thymine or cytosine (where dimer formation is possible). Equivalent levels of UV-induced mutagenesis were observed at both kinds of sites. This observation demonstrates that there is no requirement for a pyrimidine dimer directly at the site of UV-induced mutation in this single-stranded DNA phage. UV irradiation of the phage was also performed in the presence of Ag + ions, which specifically sensitize the DNA to dimer formation. The two methods of irradiation, when compared at equal survival levels (and presumably equal dimer frequencies), produced equivalent frequencies of reversion of the amber phage. We believe these results indicate that while the presence of pyrimidine dimers may be a prerequisite for UV mutagenesis, the actual mutagenic event can occur at a site some distance removed from a dimer. (orig.)

Biosynthesis of intestinal microvillar proteins. Dimerization of aminopeptidase N and lactase-phlorizin hydrolase

DEFF Research Database (Denmark)

Danielsen, E M

1990-01-01

of dimers of this enzyme therefore occurs prior to the Golgi-associated processing, and the slow rate of dimerization may be the rate-limiting step in the transport from the endoplasmic reticulum to the Golgi complex. For lactase-phlorizin hydrolase, the posttranslational processing includes a proteolytic......The pig intestinal brush border enzymes aminopeptidase N (EC 3.4.11.2) and lactase-phlorizin hydrolase (EC 3.2.1.23-62) are present in the microvillar membrane as homodimers. Dimethyl adipimidate was used to cross-link the two [35S]methionine-labeled brush border enzymes from cultured mucosal...... explants. For aminopeptidase N, dimerization did not begin until 5-10 min after synthesis, and maximal dimerization by cross-linking of the transient form of the enzyme required 1 h, whereas the mature form of aminopeptidase N cross-linked with unchanged efficiency from 45 min to 3 h of labeling. Formation...

GLYCOLALDEHYDE FORMATION VIA THE DIMERIZATION OF THE FORMYL RADICAL

Energy Technology Data Exchange (ETDEWEB)

Woods, Paul M.; Viti, Serena [Department of Physics and Astronomy, University College London, Gower Street, London WC1E 6BT (United Kingdom); Slater, Ben; Raza, Zamaan; Brown, Wendy A.; Burke, Daren J., E-mail: p.woods@qub.ac.uk [Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ (United Kingdom)

2013-11-10

Glycolaldehyde, the simplest monosaccharide sugar, has recently been detected in low- and high-mass star-forming cores. Following our previous investigation into glycolaldehyde formation, we now consider a further mechanism for the formation of glycolaldehyde that involves the dimerization of the formyl radical, HCO. Quantum mechanical investigation of the HCO dimerization process upon an ice surface is predicted to be barrierless and therefore fast. In an astrophysical context, we show that this mechanism can be very efficient in star-forming cores. It is limited by the availability of the formyl radical, but models suggest that only very small amounts of CO are required to be converted to HCO to meet the observational constraints.

GLYCOLALDEHYDE FORMATION VIA THE DIMERIZATION OF THE FORMYL RADICAL

International Nuclear Information System (INIS)

Woods, Paul M.; Viti, Serena; Slater, Ben; Raza, Zamaan; Brown, Wendy A.; Burke, Daren J.

2013-01-01

Glycolaldehyde, the simplest monosaccharide sugar, has recently been detected in low- and high-mass star-forming cores. Following our previous investigation into glycolaldehyde formation, we now consider a further mechanism for the formation of glycolaldehyde that involves the dimerization of the formyl radical, HCO. Quantum mechanical investigation of the HCO dimerization process upon an ice surface is predicted to be barrierless and therefore fast. In an astrophysical context, we show that this mechanism can be very efficient in star-forming cores. It is limited by the availability of the formyl radical, but models suggest that only very small amounts of CO are required to be converted to HCO to meet the observational constraints

Acylphenols and dimeric acylphenols from Myristica maxima Warb.

Science.gov (United States)

Othman, Muhamad Aqmal; Sivasothy, Yasodha; Looi, Chung Yeng; Ablat, Abdulwali; Mohamad, Jamaludin; Litaudon, Marc; Awang, Khalijah

2016-06-01

Giganteone E (1), a new dimeric acylphenol was isolated as a minor constituent from the bark of Myristica maxima Warb. The structure of 1 was established on the basis of 1D and 2D NMR techniques and LCMS-IT-TOF analysis. Malabaricones A-C (2-4), giganteones A and C (5 and 6), maingayones A and B (7 and 8), maingayic acid B (9) and β-sitosteryl oleate (10) were also characterized in this plant for the first time. Compound 10 was identified for the first time in the Myristicaceae. Compounds 2 and 5 were active against human prostate cancer cell-lines, thus making this the first report on the prostate cancer inhibiting potential of acylphenols and dimeric acylphenols. Compounds 1, 4, 5, 7 and 8 exhibited potent DPPH free radical scavenging activity. This is the first report on their free radical scavenging capacity. Copyright © 2016. Published by Elsevier B.V.

Cardiac Calcium ATPase Dimerization Measured by Cross-Linking and Fluorescence Energy Transfer.

Science.gov (United States)

Blackwell, Daniel J; Zak, Taylor J; Robia, Seth L

2016-09-20

The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homooligomers that increase the catalytic rate of calcium transport. We investigated SERCA dimerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher-molecular-weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer measurements in cells transiently transfected with fluorescently labeled SERCA2a revealed that SERCA readily forms homodimers. These dimers formed in the absence or presence of the SERCA regulatory partner, phospholamban (PLB) and were unaltered by PLB phosphorylation or changes in calcium or ATP. Fluorescence lifetime data are compatible with a model in which PLB interacts with a SERCA homodimer in a stoichiometry of 1:2. Together, these results suggest that SERCA forms constitutive homodimers in live cells and that dimer formation is not modulated by SERCA conformational poise, PLB binding, or PLB phosphorylation. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Analysis of hepatitis C virus RNA dimerization and core–RNA interactions

Science.gov (United States)

Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

2006-01-01

The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3′-untranslated region (3′-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623–2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3′-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus. PMID:16707664

Analysis of hepatitis C virus RNA dimerization and core-RNA interactions.

Science.gov (United States)

Ivanyi-Nagy, Roland; Kanevsky, Igor; Gabus, Caroline; Lavergne, Jean-Pierre; Ficheux, Damien; Penin, François; Fossé, Philippe; Darlix, Jean-Luc

2006-01-01

The core protein of hepatitis C virus (HCV) has been shown previously to act as a potent nucleic acid chaperone in vitro, promoting the dimerization of the 3'-untranslated region (3'-UTR) of the HCV genomic RNA, a process probably mediated by a small, highly conserved palindromic RNA motif, named DLS (dimer linkage sequence) [G. Cristofari, R. Ivanyi-Nagy, C. Gabus, S. Boulant, J. P. Lavergne, F. Penin and J. L. Darlix (2004) Nucleic Acids Res., 32, 2623-2631]. To investigate in depth HCV RNA dimerization, we generated a series of point mutations in the DLS region. We find that both the plus-strand 3'-UTR and the complementary minus-strand RNA can dimerize in the presence of core protein, while mutations in the DLS (among them a single point mutation that abolished RNA replication in a HCV subgenomic replicon system) completely abrogate dimerization. Structural probing of plus- and minus-strand RNAs, in their monomeric and dimeric forms, indicate that the DLS is the major if not the sole determinant of UTR RNA dimerization. Furthermore, the N-terminal basic amino acid clusters of core protein were found to be sufficient to induce dimerization, suggesting that they retain full RNA chaperone activity. These findings may have important consequences for understanding the HCV replicative cycle and the genetic variability of the virus.

Alignment and Imaging of the CS2 Dimer Inside Helium Nanodroplets

Science.gov (United States)

Pickering, James D.; Shepperson, Benjamin; Hübschmann, Bjarke A. K.; Thorning, Frederik; Stapelfeldt, Henrik

2018-03-01

The carbon disulphide (CS2) dimer is formed inside He nanodroplets and identified using fs laser-induced Coulomb explosion, by observing the CS2+ ion recoil velocity. It is then shown that a 160 ps moderately intense laser pulse can align the dimer in advantageous spatial orientations which allow us to determine the cross-shaped structure of the dimer by analysis of the correlations between the emission angles of the nascent CS2+ and S+ ions, following the explosion process. Our method will enable fs time-resolved structural imaging of weakly bound molecular complexes during conformational isomerization, including formation of exciplexes.

Structural Insights into the Association of Hif1 with Histones H2A-H2B Dimer and H3-H4 Tetramer.

Science.gov (United States)

Zhang, Mengying; Liu, Hejun; Gao, Yongxiang; Zhu, Zhongliang; Chen, Zijun; Zheng, Peiyi; Xue, Lu; Li, Jixi; Teng, Maikun; Niu, Liwen

2016-10-04

Histone chaperones are critical for guiding specific post-transcriptional modifications of histones, safeguarding the histone deposition (or disassociation) of nucleosome (dis)assembly, and regulating chromatin structures to change gene activities. HAT1-interacting factor 1 (Hif1) has been reported to be an H3-H4 chaperone and to be involved in telomeric silencing and nucleosome (dis)assembly. However, the structural basis for the interaction of Hif1 with histones remains unknown. Here, we report the complex structure of Hif1 binding to H2A-H2B for uncovering the chaperone specificities of Hif1 on binding to both the H2A-H2B dimer and the H3-H4 tetramer. Our findings reveal that Hif1 interacts with the H2A-H2B dimer and the H3-H4 tetramer via distinct mechanisms, suggesting that Hif1 is a pivotal scaffold on alternate binding of H2A-H2B and H3-H4. These specificities are conserved features of the Sim3-Hif1-NASP interrupted tetratricopeptide repeat proteins, which provide clues for investigating their potential roles in nucleosome (dis)assembly. Copyright © 2016 Elsevier Ltd. All rights reserved.

Glycine transporter dimers: evidence for occurrence in the plasma membrane

DEFF Research Database (Denmark)

Bartholomäus, Ingo; Milan-Lobo, Laura; Nicke, Annette

2008-01-01

membrane based on hydrodynamic and native gel electrophoretic studies. Here, we used cysteine substitution and oxidative cross-linking to show that of GlyT1 and GlyT2 also form dimeric complexes within the plasma membrane. GlyT oligomerization at the cell surface was confirmed for both GlyT1 and GlyT2......Different Na(+)/Cl(-)-dependent neurotransmitter transporters of the SLC6a family have been shown to form dimers or oligomers in both intracellular compartments and at the cell surface. In contrast, the glycine transporters (GlyTs) GlyT1 and -2 have been reported to exist as monomers in the plasma...

Antimicrobial peptide protegrin-3 adopt an antiparallel dimer in the presence of DPC micelles: a high-resolution NMR study

Energy Technology Data Exchange (ETDEWEB)

Usachev, K. S., E-mail: k.usachev@kpfu.ru; Efimov, S. V.; Kolosova, O. A.; Klochkova, E. A.; Aganov, A. V.; Klochkov, V. V. [Kazan Federal University, NMR Laboratory, Institute of Physics (Russian Federation)

2015-05-15

A tendency to dimerize in the presence of lipids was found for the protegrin. The dimer formation by the protegrin-1 (PG-1) is the first step for further oligomeric membrane pore formation. Generally there are two distinct model of PG-1 dimerization in either a parallel or antiparallel β-sheet. But despite the wealth of data available today, protegrin dimer structure and pore formation is still not completely understood. In order to investigate a more detailed dimerization process of PG-1 and if it will be the same for another type of protegrins, in this work we used a high-resolution NMR spectroscopy for structure determination of protegrin-3 (RGGGL-CYCRR-RFCVC-VGR) in the presence of perdeuterated DPC micelles and demonstrate that PG-3 forms an antiparallel NCCN dimer with a possible association of these dimers. This structural study complements previously published solution, solid state and computational studies of PG-1 in various environments and validate the potential of mean force simulations of PG-1 dimers and association of dimers to form octameric or decameric β-barrels.

Photoreactivation of pyrimidine dimers in the DNA of normal and xeroderma pigmentosum cells

International Nuclear Information System (INIS)

Sutherland, B.M.; Oliver, R.; Fuselier, C.O.; Sutherland, J.C.

1976-01-01

Photoproducts formed in the DNA of human cells irradiated with ultraviolet light (uv) were identified as cyclobutyl pyrimidine dimers by their chromatographic mobility, reversibility to monomers upon short wavelength uv irradiation, and comparison of the kinetics of this monomerization with that of authentic cis--syn thymine--thymine dimers prepared by irradiation of thymine in ice. The level of cellular photoreactivation of these dimers reflects the level of photoreactivating enzyme measured in cell extracts. Action spectra for cellular dimer photoreactivation in the xeroderma pigmentosum line XP12BE agree in range (300 nm to at least 577 nm) and maximum (near 400 nm) with that for photoreactivation by purified human photoreactivating enzyme. Normal human cells can also photoreactivate dimers in their DNA. The action spectrum for the cellular monomerization of dimers is similar to that for photoreactivation by the photoreactivating enzyme in extracts of normal human fibroblasts

Antioxidant and membrane effects of procyanidin dimers and trimers isolated from peanut and cocoa.

Science.gov (United States)

Verstraeten, Sandra V; Hammerstone, John F; Keen, Carl L; Fraga, César G; Oteiza, Patricia I

2005-06-15

The antioxidant and membrane effects of dimer (Dim) and trimer (Trim) procyanidins isolated from cocoa (Theobroma cacao) (B- and C-bonded) and peanut (Arachis hypogea L.) skin (A-bonded) were evaluated in phosphatidyl choline liposomes. When liposomes were oxidized with a steady source of oxidants, the above dimers and trimers inhibited to a similar extent lipid oxidation in a concentration (0.33-5 microM)-dependent manner. With respect to membrane effects, Dim A1, Dim B, Trim A, and Trim C increased (Dim A1 = Dim B and Trim A = Trim C), while Dim A2 decreased, membrane surface potential. All of the procyanidins tested decreased membrane fluidity as determined by fluorescent probes at the water-lipid interface, an effect that extended into the hydrophobic region of the bilayer. Both dimers and trimers protected the lipid bilayer from disruption by Triton X-100. The magnitude of the protection was Dim A1 > Dim A2 > Dim B and Trim C > Trim A. Thus, dimers and trimers can interact with membrane phospholipids, presumably with their polar headgroup. As a consequence of this interaction, they can provide protection against the attack of oxidants and other molecules that challenge the integrity of the bilayer.

Dimerization of human immunodeficiency virus (type 1) RNA: stimulation by cations and possible mechanism.

Science.gov (United States)

Marquet, R; Baudin, F; Gabus, C; Darlix, J L; Mougel, M; Ehresmann, C; Ehresmann, B

1991-05-11

The retroviral genome consists of two identical RNA molecules joined close to their 5' ends by the dimer linkage structure. Recent findings indicated that retroviral RNA dimerization and encapsidation are probably related events during virion assembly. We studied the cation-induced dimerization of HIV-1 RNA and results indicate that all in vitro generated HIV-1 RNAs containing a 100 nucleotide domain downstream from the 5' splice site are able to dimerize. RNA dimerization depends on the concentration of RNA, mono- and multivalent cations, the size of the monovalent cation, temperature, and pH. Up to 75% of HIV-1 RNA is dimeric in the presence of spermidine. HIV-1 RNA dimer is fairly resistant to denaturing agents and unaffected by intercalating drugs. Antisense HIV-1 RNA does not dimerize but heterodimers can be formed between HIV-1 RNA and either MoMuLV or RSV RNA. Therefore retroviral RNA dimerization probably does not simply proceed through mechanisms involving Watson-Crick base-pairing. Neither adenine and cytosine protonation, nor quartets containing only guanines appear to determine the stability of the HIV-1 RNA dimer, while quartets involving both adenine(s) and guanine(s) could account for our results. A consensus sequence PuGGAPuA found in the putative dimerization-encapsidation region of all retroviral genomes examined may participate in the dimerization process.

Dislocations and vacancies in two-dimensional mixed crystals of spheres and dimers

KAUST Repository

Gerbode, Sharon J.

2010-10-15

In colloidal crystals of spheres, dislocation motion is unrestricted. On the other hand, recent studies of relaxation in crystals of colloidal dimer particles have demonstrated that the dislocation dynamics in such crystals are reminiscent of glassy systems. The observed glassy dynamics arise as a result of dislocation cages formed by certain dimer orientations. In the current study, we use experiments and simulations to investigate the transition that arises when a pure sphere crystal is doped with an increasing concentration of dimers. Specifically, we focus on both dislocation caging and vacancy motion. Interestingly, we find that any nonzero fraction of dimers introduces finite dislocation cages, suggesting that glassy dynamics are present for any mixed crystal. However, we have also identified a vacancy-mediated uncaging mechanism for releasing dislocations from their cages. This mechanism is dependent on vacancy diffusion, which slows by orders of magnitude as the dimer concentration is increased. We propose that in mixed crystals with low dimer concentrations vacancy diffusion is fast enough to uncage dislocations and delay the onset of glassy dislocation dynamics. © 2010 The American Physical Society.

Dislocations and vacancies in two-dimensional mixed crystals of spheres and dimers

KAUST Repository

Gerbode, Sharon J.; Ong, Desmond C.; Liddell, Chekesha M.; Cohen, Itai

2010-01-01

In colloidal crystals of spheres, dislocation motion is unrestricted. On the other hand, recent studies of relaxation in crystals of colloidal dimer particles have demonstrated that the dislocation dynamics in such crystals are reminiscent of glassy systems. The observed glassy dynamics arise as a result of dislocation cages formed by certain dimer orientations. In the current study, we use experiments and simulations to investigate the transition that arises when a pure sphere crystal is doped with an increasing concentration of dimers. Specifically, we focus on both dislocation caging and vacancy motion. Interestingly, we find that any nonzero fraction of dimers introduces finite dislocation cages, suggesting that glassy dynamics are present for any mixed crystal. However, we have also identified a vacancy-mediated uncaging mechanism for releasing dislocations from their cages. This mechanism is dependent on vacancy diffusion, which slows by orders of magnitude as the dimer concentration is increased. We propose that in mixed crystals with low dimer concentrations vacancy diffusion is fast enough to uncage dislocations and delay the onset of glassy dislocation dynamics. © 2010 The American Physical Society.

Proteolysis of truncated hemolysin A yields a stable dimerization interface

Energy Technology Data Exchange (ETDEWEB)

Novak, Walter R.P.; Bhattacharyya, Basudeb; Grilley, Daniel P.; Weaver, Todd M. (Wabash); (UW)

2017-02-21

Wild-type and variant forms of HpmA265 (truncated hemolysin A) fromProteus mirabilisreveal a right-handed, parallel β-helix capped and flanked by segments of antiparallel β-strands. The low-salt crystal structures form a dimeric structureviathe implementation of on-edge main-chain hydrogen bonds donated by residues 243–263 of adjacent monomers. Surprisingly, in the high-salt structures of two variants, Y134A and Q125A-Y134A, a new dimeric interface is formedviamain-chain hydrogen bonds donated by residues 203–215 of adjacent monomers, and a previously unobserved tetramer is formed. In addition, an eight-stranded antiparallel β-sheet is formed from the flap regions of crystallographically related monomers in the high-salt structures. This new interface is possible owing to additional proteolysis of these variants after Tyr240. The interface formed in the high-salt crystal forms of hemolysin A variants may mimic the on-edge β-strand positioning used in template-assisted hemolytic activity.

Investigation of split-off dimers on the Si(001)2x1 surface

International Nuclear Information System (INIS)

Schofield, S.R.; O'Brien, J.L.; Curson, N.J.; Simmons, M.Y.; Clark, R.G.

2002-01-01

Full text: A detailed knowledge of the nature of crystalline defects on the Si(001)2x1 surface is becoming increasingly important as more research effort is dedicated to producing atomic-scale electronic devices. Here we present high-resolution scanning tunnelling microscopy (STM) images and ab initio pseudopotential calculations of an unusual defect of the silicon (001) surface called the split-off dimer. In high-resolution filled-state images, split-off dimers appear as a pair of protrusions, in contrast to the surrounding surface dimers that appear as 'bean-shaped' protrusions. We show that π-bonding does not exist between the atoms of the split-off dimer, but instead, the dimer atoms form π-bonds with two second layer atoms as part of a tetramer bonding arrangement. We discuss the strain associated with split-off dimer defects and describe how this strain significantly affects the bonding arrangements and local density of states around these defects

Analytical study of avian reticuloendotheliosis virus dimeric RNA generated in vivo and in vitro.

Science.gov (United States)

Darlix, J L; Gabus, C; Allain, B

1992-12-01

The retroviral genome consists of two identical RNA molecules associated at their 5' ends by a stable structure called the dimer linkage structure. The dimer linkage structure, while maintaining the dimer state of the retroviral genome, might also be involved in packaging and reverse transcription, as well as recombination during proviral DNA synthesis. To study the dimer structure of the retroviral genome and the mechanism of dimerization, we analyzed features of the dimeric genome of reticuloendotheliosis virus (REV) type A and identified elements required for its dimerization. Here we report that the REV dimeric genome extracted from virions and infected cells, as well as that synthesized in vitro, is more resistant to heat denaturation than avian sarcoma and leukemia virus, murine leukemia virus, or human immunodeficiency virus type 1 dimeric RNA. The minimal domain required to form a stable REV RNA dimer in vitro was found to map between positions 268 and 452 (KpnI and SalI sites), thus corresponding to the E encapsidation sequence (J. E. Embretson and H. M. Temin, J. Virol. 61:2675-2683, 1987). In addition, both the 5' and 3' halves of E are necessary in cis for RNA dimerization and the extent of RNA dimerization is influenced by viral sequences flanking E. Rapid and efficient dimerization of REV RNA containing gag sequences in addition to the E sequences and annealing of replication primer tRNA(Pro) to the primer-binding site necessitate the nucleocapsid protein.

Sigma- versus Pi-Dimerization Modes of Triangulene.

Science.gov (United States)

Mou, Zhongyu; Kertesz, Miklos

2018-04-20

We show that the diradicaloid triangulene, a graphene nano-flake molecule, can aggregate in a variety of dimerization modes. We found by density functional theory modeling a number of triangulene dimers including six doubly bonded σ-dimers in addition to the previously reported six pancake bonded π-dimer isomers. The σ-dimers display a wide range of stabilities: the interaction energy of the most stable σ-dimer is -25.17 kcal mol -1 . Besides the doubly bonded σ-dimers with closed shell ground states, we also found an open-shell singly σ-bonded diradicaloid dimer. We found an interesting isomerization route between a doubly bonded σ-dimer, a singly bonded σ-dimer with a low-lying triplet state and two π-bonded dimers with low-lying quintet states. Derivatives of triangulene, trioxo-triangulenes (TOTs) have been previously characterized experimentally. Here, we show the reasons why so far only the π-dimer but not the σ-dimer was experimentally observed for all TOTs. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The induction and repair of cyclobutane thymidine dimers in human skin

International Nuclear Information System (INIS)

Roza, L.; Erasmus Univ., Rotterdam; Vermeulen, W.; Schans, G.P. van der; Lohman, P.H.M.

1987-01-01

The most important detrimental effect of ultraviolet radiation (UV) on the living cell, so far known, is the induction of damage in the DNA. The major photoproducts induced in DNA by UV-C (200-280 nm) and UV-B (280-315 nm) are the cyclobutane-type pyrimidine dimers, which have been implicated in UV-induced mutagenesis and carcinogenesis. Dimer lesions in DNA of cells may be repaired in the dark by a multi-enzyme process (excision repair), or via a light dependent enzymatic reaction known as photoreactivation (phr) which is specific for pyrimidine dimers. Although phr has been found to occur in a wide range of organisms, studies on the presence of phr in mammalian cells have yielded conflicting results. To investigate repair of pyrimidine dimers in human skin cells irradiated in vivo, a specific and sensitive detection method was developed based on a monoclonal antibody directed against thymidine dimers. Application together with a fluorescent immunostaining permits the direct detection of thymidine dimers in human skin cells. The method is used in studies aimed at a better understanding of the role of these lesions in the process of carcinogenesis. A report is given on the isolation and characterization of the antibodies, and their application in a study on the induction of pyrimidine dimers in human skin and on photorepair in cultured cells. 10 refs.; 2 figs

The EBNA-2 N-Terminal Transactivation Domain Folds into a Dimeric Structure Required for Target Gene Activation.

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Anders Friberg

2015-05-01

Full Text Available Epstein-Barr virus (EBV is a γ-herpesvirus that may cause infectious mononucleosis in young adults. In addition, epidemiological and molecular evidence links EBV to the pathogenesis of lymphoid and epithelial malignancies. EBV has the unique ability to transform resting B cells into permanently proliferating, latently infected lymphoblastoid cell lines. Epstein-Barr virus nuclear antigen 2 (EBNA-2 is a key regulator of viral and cellular gene expression for this transformation process. The N-terminal region of EBNA-2 comprising residues 1-58 appears to mediate multiple molecular functions including self-association and transactivation. However, it remains to be determined if the N-terminus of EBNA-2 directly provides these functions or if these activities merely depend on the dimerization involving the N-terminal domain. To address this issue, we determined the three-dimensional structure of the EBNA-2 N-terminal dimerization (END domain by heteronuclear NMR-spectroscopy. The END domain monomer comprises a small fold of four β-strands and an α-helix which form a parallel dimer by interaction of two β-strands from each protomer. A structure-guided mutational analysis showed that hydrophobic residues in the dimer interface are required for self-association in vitro. Importantly, these interface mutants also displayed severely impaired self-association and transactivation in vivo. Moreover, mutations of solvent-exposed residues or deletion of the α-helix do not impair dimerization but strongly affect the functional activity, suggesting that the EBNA-2 dimer presents a surface that mediates functionally important intra- and/or intermolecular interactions. Our study shows that the END domain is a novel dimerization fold that is essential for functional activity. Since this specific fold is a unique feature of EBNA-2 it might provide a novel target for anti-viral therapeutics.

2-Ethynylpyridine dimers: IR spectroscopic and computational study

Science.gov (United States)

Bakarić, Danijela; Spanget-Larsen, Jens

2018-04-01

2-ethynylpyridine (2-EP) presents a multifunctional system capable of participation in hydrogen-bonded complexes utilizing hydrogen bond donating (tbnd Csbnd H, Aryl-H) and hydrogen bond accepting functions (N-atom, Ctbnd C and pyridine π-systems). In this work, IR spectroscopy and theoretical calculations are used to study possible 2-EP dimer structures as well as their distribution in an inert solvent such as tetrachloroethene. Experimentally, the tbnd Csbnd H stretching vibration of the 2-EP monomer absorbs close to 3300 cm-1, whereas a broad band with maximum around 3215 cm-1 emerges as the concentration rises, indicating the formation of hydrogen-bonded complexes involving the tbnd Csbnd H moiety. The Ctbnd C stretching vibration of monomer 2-EP close to 2120 cm-1 is, using derivative spectroscopy, resolved from the signals of the dimer complexes with maximum around 2112 cm-1. Quantum chemical calculations using the B3LYP + D3 model with counterpoise correction predict that the two most stable dimers are of the π-stacked variety, closely followed by dimers with intermolecular tbnd Csbnd H⋯N hydrogen bonding; the predicted red shifts of the tbnd Csbnd H stretching wavenumbers due to hydrogen bonding are in the range 54-120 cm-1. No species with obvious hydrogen bonding involving the Ctbnd C or pyridine π-systems as acceptors are predicted. Dimerization constant at 25 °C is estimated to be K2 = 0.13 ± 0.01 mol-1 dm3.

Ab initio and matrix isolation study of the acetylene-furan dimer

International Nuclear Information System (INIS)

Sanchez-Garcia, Elsa; Mardyukov, Artur; Tekin, Adem; Crespo-Otero, Rachel; Montero, Luis A.; Sander, Wolfram; Jansen, Georg

2008-01-01

Five acetylene-furan dimer structures are identified using ab initio calculations at the second-order Moller-Plesset (MP2) level of theory. The structures are stabilized by two basic types of intermolecular interactions: the CH...O and the CH...π interaction. The CH...π interaction appears in two variants, depending on which molecule provides the hydrogen atom and which molecule the π system. The MP2 results indicate that the CH...π interaction between one of the hydrogen atoms of acetylene and the π system of furan as found in structure A is the strongest interaction, followed by the in-plane CH...O interaction in the second most stable acetylene-furan dimer structure B. A matrix isolation study shows the acetylene-furan dimer to exist in an argon matrix, but likely rather as structure B than as A. High level coupled cluster calculations with up to triple excitations (CCSD(T)) yield the interaction energy of structure A as about -2.4 kcal/mol in the complete basis set limit and find structure B to be nearly isoenergetic with -2.3 kcal/mol. This is confirmed in calculations employing the density functional theory combined with symmetry adapted intermolecular perturbation theory (DFT-SAPT) approach yielding interaction energies of -2.3 and -2.0 kcal/mol for A and B, respectively. DFT-SAPT also helps to understand the importance of the electrostatic, induction and dispersion interaction energies and their respective exchange counterparts for the stability of the various acetylene-furan dimer structures. The CH...O and CH...π interactions are furthermore analyzed with the help of the atoms in molecules (AIM) theory

Isolation of dimeric, trimeric, tetrameric and pentameric procyanidins from unroasted cocoa beans (Theobroma cacao L.) using countercurrent chromatography.

Science.gov (United States)

Esatbeyoglu, Tuba; Wray, Victor; Winterhalter, Peter

2015-07-15

The main procyanidins, including dimeric B2 and B5, trimeric C1, tetrameric and pentameric procyanidins, were isolated from unroasted cocoa beans (Theobroma cacao L.) using various techniques of countercurrent chromatography, such as high-speed countercurrent chromatography (HSCCC), low-speed rotary countercurrent chromatography (LSRCCC) and spiral-coil LSRCCC. Furthermore, dimeric procyanidins B1 and B7, which are not present naturally in the analysed cocoa beans, were obtained after semisynthesis of cocoa bean polymers with (+)-catechin as nucleophile and separated by countercurrent chromatography. In this way, the isolation of dimeric procyanidin B1 in considerable amounts (500mg, purity>97%) was possible in a single run. This is the first report concerning the isolation and semisynthesis of dimeric to pentameric procyanidins from T. cacao by countercurrent chromatography. Additionally, the chemical structures of tetrameric (cinnamtannin A2) and pentameric procyanidins (cinnamtannin A3) were elucidated on the basis of (1)H NMR spectroscopy. Interflavanoid linkage was determined by NOE-correlations, for the first time. Copyright © 2015 Elsevier Ltd. All rights reserved.

Structural features of the KPI domain control APP dimerization, trafficking, and processing.

Science.gov (United States)

Ben Khalifa, Naouel; Tyteca, Donatienne; Marinangeli, Claudia; Depuydt, Mathieu; Collet, Jean-François; Courtoy, Pierre J; Renauld, Jean-Christophe; Constantinescu, Stefan; Octave, Jean-Noël; Kienlen-Campard, Pascal

2012-02-01

The two major isoforms of human APP, APP695 and APP751, differ by the presence of a Kunitz-type protease inhibitor (KPI) domain in the extracellular region. APP processing and function is thought to be regulated by homodimerization. We used bimolecular fluorescence complementation (BiFC) to study dimerization of different APP isoforms and mutants. APP751 was found to form significantly more homodimers than APP695. Mutation of dimerization motifs in the TM domain did not affect fluorescence complementation, but native folding of KPI is critical for APP751 homodimerization. APP751 and APP695 dimers were mostly localized at steady state in the Golgi region, suggesting that most of the APP751 and 695 dimers are in the secretory pathway. Mutation of the KPI led to the retention of the APP homodimers in the endoplasmic reticulum. We finally showed that APP751 is more efficiently processed through the nonamyloidogenic pathway than APP695. These findings provide new insight on the particular role of KPI domain in APP dimerization. The correlation observed between dimerization, subcellular localization, and processing suggests that dimerization acts as an efficient regulator of APP trafficking in the secretory compartments that has major consequences on its processing.

Structure of a rabbit muscle fructose-1, 6-bisphosphate aldolase A dimer variant

Energy Technology Data Exchange (ETDEWEB)

Sherawat, Manashi [Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118-2394 (United States); Tolan, Dean R., E-mail: tolan@bu.edu [Department of Biology, Boston University, 5 Cummington Street, Boston, MA 02215 (United States); Allen, Karen N., E-mail: tolan@bu.edu [Department of Physiology and Biophysics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118-2394 (United States)

2008-05-01

The X-ray crystallographic structure of a dimer variant of fructose-1, 6-bisphosphate aldolase demonstrates a stable oligomer that mirrors half of the native tetramer. The presence of product demonstrates that this is an active form. Fructose-1, 6-bisphosphate aldolase (aldolase) is an essential enzyme in glycolysis and gluconeogenesis. In addition to this primary function, aldolase is also known to bind to a variety of other proteins, a property that may allow it to perform ‘moonlighting’ roles in the cell. Although monomeric and dimeric aldolases possess full catalytic activity, the enzyme occurs as an unusually stable tetramer, suggesting a possible link between the oligomeric state and these noncatalytic cellular roles. Here, the first high-resolution X-ray crystal structure of rabbit muscle D128V aldolase, a dimeric form of aldolase mimicking the clinically important D128G mutation in humans associated with hemolytic anemia, is presented. The structure of the dimer was determined to 1.7 Å resolution with the product DHAP bound in the active site. The turnover of substrate to produce the product ligand demonstrates the retention of catalytic activity by the dimeric aldolase. The D128V mutation causes aldolase to lose intermolecular contacts with the neighboring subunit at one of the two interfaces of the tetramer. The tertiary structure of the dimer does not significantly differ from the structure of half of the tetramer. Analytical ultracentrifugation confirms the occurrence of the enzyme as a dimer in solution. The highly stable structure of aldolase with an independent active site is consistent with a model in which aldolase has evolved as a multimeric scaffold to perform other noncatalytic functions.

T- and B-cell response analysis following calf immunisation with experimental Mycoplasma bovis vaccine containing saponin and lysozyme dimer

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Dudek Katarzyna

2017-12-01

Full Text Available Introduction:Mycoplasma bovis is a well-known cause of various disorders in cattle, such as pneumonia, arthritis, mastitis kerato-conjunctivitis, pharyngitis, laryngitis, otitis media, meningitis, and reproductive disorders. There are no commercial vaccines against M. bovis in Europe, therefore, experimental ones are still under investigation. The aim of this study was to evaluate the effect of experimental M. bovis vaccine, containing the Polish field M. bovis strain as well as saponin and lysozyme dimer adjuvants, on the T- and B-cell response in calves.

2-Ethynylpyridine dimers

DEFF Research Database (Denmark)

Bakarić, Danijela; Spanget-Larsen, Jens

2018-01-01

are used to study possible 2-EP dimer structures as well as their distribution in an inert solvent such as tetrachloroethene. Experimentally, the ≡C–H stretching vibration of the 2-EPmonomer absorbs close to 3300 cm−1, whereas a broad band withmaximum around 3215 cm−1 emerges as the concentration rises...... model with counterpoise correction predict that the two most stable dimers are of the pi-stacked variety, closely followed by dimers with intermolecular ≡C–H···N hydrogen bonding; the predicted red shifts of the ≡C–H stretching wavenumbers due to hydrogen bonding are in the range 54 – 120 cm–1...

pi-Dimers of end-capped oligopyrrole cation radicals

NARCIS (Netherlands)

Haare, van J.A.E.H.; Groenendaal, L.; Havinga, E.E.; Janssen, R.A.J.; Meijer, E.W.

1996-01-01

In two consecutive one-electron oxidations, oligopyrroles substituted with phenyl capping groups (PhPynPh, n = 2–4) can be oxidized reversibly to give stable cation radicals and dications. Spectroelectrochemical studies give direct evidence that diamagnetic p-dimers of cation radicals are formed in

Kinetics of the monomer-dimer reaction of yeast hexokinase PI.

Science.gov (United States)

Hoggett, J G; Kellett, G L

1992-10-15

Kinetic studies of the glucose-dependent monomer-dimer reaction of yeast hexokinase PI at pH 8.0 in the presence of 0.1 M-KCl have been carried out using the fluorescence temperature-jump technique. A slow-relaxation effect was observed which was attributed from its dependence on enzyme concentration to the monomer-dimer reaction; the reciprocal relaxation times tau-1 varied from 3 s-1 at low concentrations of glucose to 42 s-1 at saturating concentrations. Rate constants for association (kass.) and dissociation (kdiss.) were determined as a function of glucose concentration using values of the equilibrium association constant of the monomer-dimer reaction derived from sedimentation ultracentrifugation studies under similar conditions, and also from the dependence of tau-2 on enzyme concentration. kass. was almost independent of glucose concentration and its value (2 x 10(5) M-1.s-1) was close to that expected for a diffusion-controlled process. The influence of glucose on the monomer-dimer reaction is entirely due to effects on kdiss., which increases from 0.21 s-1 in the absence of glucose to 25 s-1 at saturating concentrations. The monomer and dimer forms of hexokinase have different affinities and Km values for glucose, and the results reported here imply that there may be a significant lag in the response of the monomer-dimer reaction to changes in glucose concentrations in vivo with consequent hysteretic effects on the hexokinase activity.

Quantitative Experimental Determination of Primer-Dimer Formation Risk by Free-Solution Conjugate Electrophoresis

Science.gov (United States)

Desmarais, Samantha M.; Leitner, Thomas; Barron, Annelise E.

2012-01-01

DNA barcodes are short, unique ssDNA primers that “mark” individual biomolecules. To gain better understanding of biophysical parameters constraining primer-dimer formation between primers that incorporate barcode sequences, we have developed a capillary electrophoresis method that utilizes drag-tag-DNA conjugates to quantify dimerization risk between primer-barcode pairs. Results obtained with this unique free-solution conjugate electrophoresis (FSCE) approach are useful as quantitatively precise input data to parameterize computation models of dimerization risk. A set of fluorescently labeled, model primer-barcode conjugates were designed with complementary regions of differing lengths to quantify heterodimerization as a function of temperature. Primer-dimer cases comprised two 30-mer primers, one of which was covalently conjugated to a lab-made, chemically synthesized poly-N-methoxyethylglycine drag-tag, which reduced electrophoretic mobility of ssDNA to distinguish it from ds primer-dimers. The drag-tags also provided a shift in mobility for the dsDNA species, which allowed us to quantitate primer-dimer formation. In the experimental studies, pairs of oligonucleotide primer-barcodes with fully or partially complementary sequences were annealed, and then separated by free-solution conjugate CE at different temperatures, to assess effects on primer-dimer formation. When less than 30 out of 30 basepairs were bonded, dimerization was inversely correlated to temperature. Dimerization occurred when more than 15 consecutive basepairs formed, yet non-consecutive basepairs did not create stable dimers even when 20 out of 30 possible basepairs bonded. The use of free-solution electrophoresis in combination with a peptoid drag-tag and different fluorophores enabled precise separation of short DNA fragments to establish a new mobility shift assay for detection of primer-dimer formation. PMID:22331820

Detectability of H2-Ar and H2-Ne Dimers in Jovian Atmospheres

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Young-Key Minn

1997-12-01

Full Text Available The detection of jovian hydrogen-hydrogen dimers through the clear telluric 2-micron window(Kim et al. 1995, Trafton et al. 1997 suggests possibility to detect noble gases in the form of dimer with hydrogen in jovian atmospheres. Since noble gases do not have spectral structures in the infrared, it has been difficult to derive their abundances in the atmospheres of jovian planets. If there is a significant component of noble gases other than helium in the jovian atmospheres. it might be detected through its dimer spectrum with hydrogen molecule. The relatively sharp spectral structures of hydrogen-argon and hydrogen-neon dimers compared with those of hydrogen-hydrogen dimers are useful for the detection, if an adequate signal-to-noise (S/N is obtained. If we use a large telescope, such as the Keck telescope, with a long exposure time (>24 hours, then H2-Ar spectral structure may be detected.

DFT approach to (benzylthio)acetic acid: Conformational search, molecular (monomer and dimer) structure, vibrational spectroscopy and some electronic properties

Science.gov (United States)

Sienkiewicz-Gromiuk, Justyna

2018-01-01

The DFT studies were carried out with the B3LYP method utilizing the 6-31G and 6-311++G(d,p) basis sets depending on whether the aim of calculations was to gain the geometry at equilibrium, or to calculate the optimized molecular structure of (benzylthio)acetic acid (Hbta) in the forms of monomer and dimer. The minimum conformational energy search was followed by the potential energy surface (PES) scan of all rotary bonds existing in the acid molecule. The optimized geometrical monomeric and dimeric structures of the title compound were compared with the experimental structural data in the solid state. The detailed vibrational interpretation of experimental infrared and Raman bands was performed on the basis of theoretically simulated ESFF-scaled wavenumbers calculated for the monomer and dimer structures of Hbta. The electronic characteristics of Hbta is also presented in terms of Mulliken atomic charges, frontier molecular orbitals and global reactivity descriptors. Additionally, the MEP and ESP surfaces were computed to predict coordination sites for potential metal complex formation.

Rubidium dimers in paraffin-coated cells

International Nuclear Information System (INIS)

Acosta, V M; Windes, D; Corsini, E; Ledbetter, M P; Karaulanov, T; Budker, D; Jarmola, A; Auzinsh, M; Rangwala, S A; Jackson Kimball, D F

2010-01-01

Measurements were made to determine the density of rubidium dimer vapor in paraffin-coated cells. The number density of dimers and atoms in similar paraffin-coated and uncoated cells was measured by optical spectroscopy. Due to the relatively low melting point of paraffin, a limited temperature range of 43-80 0 C was explored, with the lower end corresponding to a dimer density of less than 10 7 cm -3 . With 1 min integration time, a sensitivity to dimer number density of better than 10 6 cm -3 was achieved. No significant difference in dimer density between the cells was observed.

Dimers in nucleating vapors

Science.gov (United States)

Lushnikov, A. A.; Kulmala, M.

1998-09-01

The dimer stage of nucleation may affect considerably the rate of the nucleation process at high supersaturation of the nucleating vapor. Assuming that the dimer formation limits the nucleation rate, the kinetics of the particle formation-growth process is studied starting with the definition of dimers as bound states of two associating molecules. The partition function of dimer states is calculated by summing the Boltzmann factor over all classical bound states, and the equilibrium population of dimers is found for two types of intermolecular forces: the Lennard-Jones (LJ) and rectangular well+hard core (RW) potentials. The principle of detailed balance is used for calculating the evaporation rate of dimers. The kinetics of the particle formation-growth process is then investigated under the assumption that the trimers are stable with respect to evaporation and that the condensation rate is a power function of the particle mass. If the power exponent λ=n/(n+1) (n is a non-negative integer), the kinetics of the process is described by a finite set of moments of particle mass distribution. When the characteristic time of the particle formation by nucleation is much shorter than that of the condensational growth, n+2 universal functions of a nondimensional time define the kinetic process. These functions are calculated for λ=2/3 (gas-to-particle conversion in the free molecular regime) and λ=1/2 (formation of islands on surfaces).

Analysis of the dimerized Sb/Si(001)-(2x1) surface by x-ray standing waves

International Nuclear Information System (INIS)

Lyman, P.F.; Qian, Y.; Bedzyk, M.J.

1994-12-01

X-ray standing wave measurements were undertaken to study the bonding position of Sb adatoms on the Sb-saturated Si(001)-(2x1) surface. Using the (004) and (022) Bragg reflections, the authors find that the Sb atoms form dimers, and that the center of the Sb ad-dimers lies 1.64 angstrom above the bulk-like Si(004) surface atomic plane. These in-plane results are compared to two structural models consisting of dimers whose bonds are parallel to the surface plane and whose centers are either shifted or unshifted (parallel to the dimer bond direction) relative to the underlying substrate planes. The authors thus find two special cases consistent with these data: one with symmetric (unshifted) dimers having a dimer bond length of 2.81 angstrom, and the other with midpoint-shifted dimers, having a bond length of 2.88 angstrom and a lateral shift of 0.21 angstrom

UV-B-inducible and temperature-sensitive photoreactivation of cyclobutane pyrimidine dimers in Arabidopsis thaliana

International Nuclear Information System (INIS)

Pang, Qishen; Hays, J.B.

1991-01-01

Removal of cyclobutane pyrimidine dimers (CBPDs) in vivo from the DNA of UV-irradiated eight-leaf seedlings of Arabidopsis thaliana was rapid in the presence of visible light (half-life about 1 hour); removal of CBPDs in the dark, presumably via excision repair, was an order of magnitude slower. Extracts of plants contained significant photolyase in vitro, as assayed by restoration of transforming activity to UV-irradiated Escherichia coli plasmids; activity was maximal from four-leaf to 12-leaf stages. UV-B treatment of seedlings for 6 hours increased photolyase specific activity in extracts twofold. Arabidopsis photolyase was markedly temperature-sensitive, both in vitro (half-life at 30C about 12 minutes) and in vivo (half-life at 30C, 30 to 45 minutes). The wavelength dependency of the photoreactivation cross-section showed a broad peak at 375 to 400 nm, and is thus similar to that for maize pollen; it overlaps bacterial and yeast photolyase action spectra

Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease.

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Martin Zühlsdorf

2015-07-01

Full Text Available Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such constitutes a promising drug target. In solution, a dynamic equilibrium exists between an inactive monomeric and an active dimeric form of the enzyme, which is believed to play a key regulatory role in the orchestration of proteolysis and capsid assembly. Currently available crystal structures of herpesvirus proteases correspond either to the dimeric state or to complexes with peptide mimetics that alter the dimerization interface. In contrast, the structure of the native monomeric state has remained elusive. Here, we present the three-dimensional structures of native monomeric, active dimeric, and diisopropyl fluorophosphate-inhibited dimeric protease derived from pseudorabies virus, an alphaherpesvirus of swine. These structures, solved by X-ray crystallography to respective resolutions of 2.05, 2.10 and 2.03 Å, allow a direct comparison of the main conformational states of the protease. In the dimeric form, a functional oxyanion hole is formed by a loop of 10 amino-acid residues encompassing two consecutive arginine residues (Arg136 and Arg137; both are strictly conserved throughout the herpesviruses. In the monomeric form, the top of the loop is shifted by approximately 11 Å, resulting in a complete disruption of the oxyanion hole and loss of activity. The dimerization-induced allosteric changes described here form the physical basis for the concentration-dependent activation of the protease, which is essential for proper virus replication. Small-angle X-ray scattering experiments confirmed a concentration-dependent equilibrium of monomeric and dimeric protease in solution.

Quantitation of pyrimidine dimers in DNA from UVB-irradiated alfalfa (Medicago sativa L.) seedlings

International Nuclear Information System (INIS)

Quaite, F.E.; Sutherland, B.M.; Sutherland, J.C.

1991-01-01

Depletion of stratospheric ozone will increase the solar ultraviolet radiation in the range from 290-320 nm (UVB) that reaches the surface of the earth, placing an increased UV burden on exposed organisms. One consequence of increased UVB may be decreased productivity of crop plants. A principal lesion caused by UV in DNA is the cyclobutyl pyrimidine dimer. We have adapted a method for measuring these dimers in nanogram quantities of non-radioactive DNA for use in UV-irradiated plants. We find that biologically relevant doses of broad band UVB radiation induce easily detectable frequencies of pyrimidine dimers in the DNA of irradiated alfalfa sprout leaves and that the dose response for dimer formation is linear up to doses of at least 690 J/m 2 . We also find easily measurable frequencies of dimers in the leaves of seedlings grown in glass filtered sunlight but not exposed to additional UVB, suggesting that significant number of dimers are formed in plants exposed to normal sunlight. 27 refs., 3 figs., 1 tab

Cyclodextrin dimers as receptor molecules for steroid sensors

NARCIS (Netherlands)

de Jong, M.R.; Engbersen, Johannes F.J.; Huskens, Jurriaan; Reinhoudt, David

2000-01-01

The dansyl-modified dimer 9 complexes strongly with the steroidal bile salts. Relative to native -cyclodextrin, the binding of cholate (1 a) and deoxycholate (1 b) salts is especially enhanced. These steroids bind exclusively in a 1:1 fashion. For other bile salts (1 c-1 e) both 1:1 and 1:2

Designer interface peptide grafts target estrogen receptor alpha dimerization

International Nuclear Information System (INIS)

Chakraborty, S.; Asare, B.K.; Biswas, P.K.; Rajnarayanan, R.V.

2016-01-01

The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

Tricriticality for dimeric Coulomb molecular crystals in ground state

Science.gov (United States)

Travěnec, Igor; Šamaj, Ladislav

2017-12-01

We study the ground-state properties of a system of dimers. Each dimer consists in a pair of equivalent charges at a fixed distance, immersed in a neutralizing homogeneous background. All charges interact pairwisely by Coulomb potential. The dimer centers form a two-dimensional rectangular lattice with the aspect ratio α\\in [0, 1] and each dimer is allowed to rotate around its center. The previous numerical simulations, made for the more general Yukawa interaction, indicate that only two basic dimer configurations can appear: either all dimers are parallel or they have two different angle orientations within alternating (checkerboard) sublattices. As the dimer size increases, two second-order phase transitions, related to two kinds of the symmetry breaking in dimer’s orientations, were reported. In this paper, we use a recent analytic method based on an expansion of the interaction energy in Misra functions which converges quickly and provides an analytic derivation of the critical behaviour. Our main result is that there exists a specific aspect ratio of the rectangular lattice α^*=0.714 106 840 000 71\\ldots which divides the space of model’s phases onto two distinct regions. If the lattice aspect ratio α>α* , we recover both types of the second-order phase transitions and find that they are of mean-field type with the critical exponent β = 1/2 . If 0.711 535≤slantα<α* , the phase transition associated with the discontinuity of dimer’s angles on alternating sublattices becomes of first order. For α=α* , the first- and second-order phase transitions meet at the tricritical point, characterized by the different critical index β = 1/4 . Such phenomenon is known from literature about the Landau theory of one-component fields, but in our two-component version the scenario is more complicated: the component which is already in the symmetry-broken state at the tricritical point also interferes and exhibits unexpectedly the mean-field singular

Designer interface peptide grafts target estrogen receptor alpha dimerization

Energy Technology Data Exchange (ETDEWEB)

Chakraborty, S. [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Asare, B.K. [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States); Biswas, P.K., E-mail: pbiswas@tougaloo.edu [Laboratory of Computational Biophysics & Bioengineering, Department of Physics, Tougaloo College, Tougaloo, MS 39174 (United States); Rajnarayanan, R.V., E-mail: rajendra@buffalo.edu [Department of Pharmacology and Toxicology, University of Buffalo, Buffalo, NY 14214 (United States)

2016-09-09

The nuclear transcription factor estrogen receptor alpha (ERα), triggered by its cognate ligand estrogen, regulates a variety of cellular signaling events. ERα is expressed in 70% of breast cancers and is a widely validated target for anti-breast cancer drug discovery. Administration of anti-estrogen to block estrogen receptor activation is still a viable anti-breast cancer treatment option but anti-estrogen resistance has been a significant bottle-neck. Dimerization of estrogen receptor is required for ER activation. Blocking ERα dimerization is therefore a complementary and alternative strategy to combat anti-estrogen resistance. Dimer interface peptide “I-box” derived from ER residues 503–518 specifically blocks ER dimerization. Recently using a comprehensive molecular simulation we studied the interaction dynamics of ERα LBDs in a homo-dimer. Based on this study, we identified three interface recognition peptide motifs LDKITDT (ERα residues 479–485), LQQQHQRLAQ (residues 497–506), and LSHIRHMSNK (residues 511–520) and reported the suitability of using LQQQHQRLAQ (ER 497–506) as a template to design inhibitors of ERα dimerization. Stability and self-aggregation of peptide based therapeutics poses a significant bottle-neck to proceed further. In this study utilizing peptide grafted to preserve their pharmacophoric recognition motif and assessed their stability and potential to block ERα mediated activity in silico and in vitro. The Grafted peptides blocked ERα mediated cell proliferation and viability of breast cancer cells but did not alter their apoptotic fate. We believe the structural clues identified in this study can be used to identify novel peptidometics and small molecules that specifically target ER dimer interface generating a new breed of anti-cancer agents. - Highlights: • Designer peptide grafts retain core molecular recognition motif during MD simulations. • Designer peptide grafts with Poly-ALA helix form stable

Intracellular transport and sorting of mutant human proinsulins that fail to form hexamers.

Science.gov (United States)

Quinn, D; Orci, L; Ravazzola, M; Moore, H P

1991-06-01

Human proinsulin and insulin oligomerize to form dimers and hexamers. It has been suggested that the ability of prohormones to self associate and form aggregates may be responsible for the sorting process at the trans-Golgi. To examine whether insulin oligomerization is required for proper sorting into regulated storage granules, we have constructed point mutations in human insulin B chain that have been previously shown to prevent formation of insulin hexamers (Brange, J., U. Ribel, J. F. Hansen, G. Dodson, M. T. Hansen, S. Havelund, S. G. Melberg, F. Norris, K. Norris, L. Snel, A. R. Sorensen, and H. O. Voight. 1988. Nature [Lond.]. 333:679-682). One mutant (B10His----Asp) allows formation of dimers but not hexamers and the other (B9Ser----Asp) prevents formation of both dimers and hexamers. The mutants were transfected into the mouse pituitary AtT-20 cells, and their ability to be sorted into regulated secretory granules was compared to wild-type insulin. We found that while B10His----Asp is sorted somewhat less efficiently than wild-type insulin as reported previously (Carroll, R. J., R. E. Hammer, S. J. Chan, H. H. Swift, A. H. Rubenstein, and D. F. Steiner. 1988. Proc. Natl. Acad. Sci. USA. 85:8943-8947; Gross, D. J., P. A. Halban, C. R. Kahn, G. C. Weir, and L. Villa-Kumaroff. 1989. Proc. Natl. Acad. Sci. USA. 86:4107-4111). B9Ser----Asp is targeted to granules as efficiently as wild-type insulin. These results indicate that self association of proinsulin into hexamers is not required for its targeting to the regulated secretory pathway.

Theoretical Research on the Mechanism of the Dimerization Reactions of Alkyl Ketene

Directory of Open Access Journals (Sweden)

Zhiguo Zhang

2013-01-01

Full Text Available A quantum chemical method was employed to investigate the mechanism of dimerization reactions of alkyl ketene. All the geometric configurations of the stationary points on the reactions path were optimized with Gaussian03 employing density functional theory at the B3LYP/6-311G++(d, p level by energy gradient technique. The transition states were also investigated through synchronous transit method, and its reasonability was confirmed by using frequency analysis and intrinsic reaction coordinate analysis. The results can be summed up as follows: according to the frontier orbital theory, the dimerization reaction (3 to generate four-membered carbon cyclic product P3 is forbidden. Two different dimerization processes of alkyl ketene are all concerted but nonsynchronous, taking place through twisted four-membered cyclic transition states. The activation energies were calculated to be 34.54 and 61.73 kJ/mol, respectively for the two ketene dimerization processes. Calculation results satisfactorily explained the experimental facts.

Mixed dimers, ch. 7

International Nuclear Information System (INIS)

Deursen, A.P.J. van; Reuss, J.

1976-01-01

An attempt has been made to detect mixed dimers in nozzle beams of mixtures; NeAr and HeNe dimers were observed with sufficient intensity to determine the total collision cross section. A similar attempt for H 2 Ar was partially hampered by the circumstance that the corresponding HAr + ion must be detected on the wing of the thousand times larger Ar + peak. The search for H 2 He, H 2 Ne and HeAr dimers was not successful, due to masking ion peaks, H 5 + for HHe + , 21 Ne + for H 20 Ne + , and CO 2 + for HeAr + . (Auth.)

c -Axis Dimer and Its Electronic Breakup: The Insulator-to-Metal Transition in Ti2 O3

Science.gov (United States)

Chang, C. F.; Koethe, T. C.; Hu, Z.; Weinen, J.; Agrestini, S.; Zhao, L.; Gegner, J.; Ott, H.; Panaccione, G.; Wu, Hua; Haverkort, M. W.; Roth, H.; Komarek, A. C.; Offi, F.; Monaco, G.; Liao, Y.-F.; Tsuei, K.-D.; Lin, H.-J.; Chen, C. T.; Tanaka, A.; Tjeng, L. H.

2018-04-01

We report on our investigation of the electronic structure of Ti2 O3 using (hard) x-ray photoelectron and soft x-ray absorption spectroscopy. From the distinct satellite structures in the spectra, we have been able to establish unambiguously that the Ti-Ti c -axis dimer in the corundum crystal structure is electronically present and forms an a1 ga1 g molecular singlet in the low-temperature insulating phase. Upon heating, we observe a considerable spectral weight transfer to lower energies with orbital reconstruction. The insulator-metal transition may be viewed as a transition from a solid of isolated Ti-Ti molecules into a solid of electronically partially broken dimers, where the Ti ions acquire additional hopping in the a -b plane via the egπ channel, the opening of which requires consideration of the multiplet structure of the on-site Coulomb interaction.

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction

Directory of Open Access Journals (Sweden)

Lukas P. Feilen

2017-05-01

Full Text Available Physiological function and pathology of the Alzheimer’s disease causing amyloid precursor protein (APP are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs. The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

Fe65-PTB2 Dimerization Mimics Fe65-APP Interaction.

Science.gov (United States)

Feilen, Lukas P; Haubrich, Kevin; Strecker, Paul; Probst, Sabine; Eggert, Simone; Stier, Gunter; Sinning, Irmgard; Konietzko, Uwe; Kins, Stefan; Simon, Bernd; Wild, Klemens

2017-01-01

Physiological function and pathology of the Alzheimer's disease causing amyloid precursor protein (APP) are correlated with its cytosolic adaptor Fe65 encompassing a WW and two phosphotyrosine-binding domains (PTBs). The C-terminal Fe65-PTB2 binds a large portion of the APP intracellular domain (AICD) including the GYENPTY internalization sequence fingerprint. AICD binding to Fe65-PTB2 opens an intra-molecular interaction causing a structural change and altering Fe65 activity. Here we show that in the absence of the AICD, Fe65-PTB2 forms a homodimer in solution and determine its crystal structure at 2.6 Å resolution. Dimerization involves the unwinding of a C-terminal α-helix that mimics binding of the AICD internalization sequence, thus shielding the hydrophobic binding pocket. Specific dimer formation is validated by nuclear magnetic resonance (NMR) techniques and cell-based analyses reveal that Fe65-PTB2 together with the WW domain are necessary and sufficient for dimerization. Together, our data demonstrate that Fe65 dimerizes via its APP interaction site, suggesting that besides intra- also intermolecular interactions between Fe65 molecules contribute to homeostatic regulation of APP mediated signaling.

FAK dimerization controls its kinase-dependent functions at focal adhesions

KAUST Repository

Brami-Cherrier, Karen; Gervasi, Nicolas; Arsenieva, Diana A.; Walkiewicz, Katarzyna; Boutterin, Marie Claude; Ortega, Á lvaro Darí o; Leonard, Paul G.; Seantier, Bastien; Gasmi, Laï la; Bouceba, Tahar; Kadaré , Gress; Girault -, Jean Antoine; Arold, Stefan T.

2014-01-01

Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK's kinase-dependent functions-autophosphorylation of tyrosine-397-requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation. © 2014 The Authors.

Tautomerization and Dimerization of 6,13-Disubstituted Derivatives of Pentacene.

Science.gov (United States)

Garcia-Borràs, Marc; Konishi, Akihito; Waterloo, Andreas; Liang, Yong; Cao, Yang; Hetzer, Constantin; Lehnherr, Dan; Hampel, Frank; Houk, Kendall N; Tykwinski, Rik R

2017-05-02

Two new 6,13-disubstituted pentacene derivatives, 1 c and 1 d, with alkyl and triisopropylsilylethynyl substitution have been synthesized and characterized experimentally and computationally. The alkyl substituted 1 c and 1 d represent the first 6-alkyl-substituted pentacene derivative where the fully aromatic species dominates over the corresponding tautomer. Indeed, no tautomerization product is found for either 1 c or 1 d upon heating or in the presence of catalytic amounts of acid. On the other hand, an unexpected dimer (3 c) is formed from 1 c. A plausible mechanism for this new dimerization process of the 6-methyl-substituted pentacene derivative 1 c is proposed, which involves first a bimolecular hydrogen atom transfer followed by an intramolecular [4+2] Diels-Alder cycloaddition. In the case of 6-butyl substitution, neither tautomerization nor dimerization is observed. Computations support the proposed 1 c dehydrodimerization pathway, explain why 1 d does not dimerize, and show the importance of the nature of the group at C-13 in controlling the relative stability of 6-alkyl-substituted pentacene tautomers. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

FAK dimerization controls its kinase-dependent functions at focal adhesions

KAUST Repository

Brami-Cherrier, Karen

2014-01-30

Focal adhesion kinase (FAK) controls adhesion-dependent cell motility, survival, and proliferation. FAK has kinase-dependent and kinase-independent functions, both of which play major roles in embryogenesis and tumor invasiveness. The precise mechanisms of FAK activation are not known. Using x-ray crystallography, small angle x-ray scattering, and biochemical and functional analyses, we show that the key step for activation of FAK\\'s kinase-dependent functions-autophosphorylation of tyrosine-397-requires site-specific dimerization of FAK. The dimers form via the association of the N-terminal FERM domain of FAK and are stabilized by an interaction between FERM and the C-terminal FAT domain. FAT binds to a basic motif on FERM that regulates co-activation and nuclear localization. FAK dimerization requires local enrichment, which occurs specifically at focal adhesions. Paxillin plays a dual role, by recruiting FAK to focal adhesions and by reinforcing the FAT:FERM interaction. Our results provide a structural and mechanistic framework to explain how FAK combines multiple stimuli into a site-specific function. The dimer interfaces we describe are promising targets for blocking FAK activation. © 2014 The Authors.

A Lys-Trp cation-π interaction mediates the dimerization and function of the chloride intracellular channel protein 1 transmembrane domain.

Science.gov (United States)

Peter, Bradley; Polyansky, Anton A; Fanucchi, Sylvia; Dirr, Heini W

2014-01-14

Chloride intracellular channel protein 1 (CLIC1) is a dual-state protein that can exist either as a soluble monomer or in an integral membrane form. The oligomerization of the transmembrane domain (TMD) remains speculative despite it being implicated in pore formation. The extent to which electrostatic and van der Waals interactions drive folding and association of the dimorphic TMD is unknown and is complicated by the requirement of interactions favorable in both aqueous and membrane environments. Here we report a putative Lys37-Trp35 cation-π interaction and show that it stabilizes the dimeric form of the CLIC1 TMD in membranes. A synthetic 30-mer peptide comprising a K37M TMD mutant was examined in 2,2,2-trifluoroethanol, sodium dodecyl sulfate micelles, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine liposomes using far-ultraviolet (UV) circular dichroism, fluorescence, and UV absorbance spectroscopy. Our data suggest that Lys37 is not implicated in the folding, stability, or membrane insertion of the TMD peptide. However, removal of this residue impairs the formation of dimers and higher-order oligomers. This is accompanied by a 30-fold loss of chloride influx activity, suggesting that dimerization modulates the rate of chloride conductance. We propose that, within membranes, individual TMD helices associate via a Lys37-mediated cation-π interaction to form active dimers. The latter findings are also supported by results of modeling a putative TMD dimer conformation in which Lys37 and Trp35 form cation-π pairs at the dimer interface. Dimeric helix bundles may then associate to form fully active ion channels. Thus, within a membrane-like environment, aromatic interactions involving a polar lysine side chain provide a thermodynamic driving force for helix-helix association.

Dimers at Ge/Si(001) surfaces: Ge coverage dependent quenching, reactivation of flip-flop motion, and interaction with dimer vacancy lines

International Nuclear Information System (INIS)

Hirayama, H.; Mizuno, H.; Yoshida, R.

2002-01-01

We studied Ge coverage (θ Ge ) dependent quenching, reactivation of the flip-flop motion, and interaction with dimer vacancy lines (DVLs) of dimers on Ge/Si(001) surfaces using a scanning tunneling microscope (STM) combined with a molecular beam epitaxy apparatus. Deposition of ∼0.3 ML (monolayer) Ge quenched the flip-flop motion, making all dimers asymmetric. Further deposition introduced DVLs at θ Ge ≥∼0.5 ML, and symmetric dimer domains appeared again locally at θ≥1.5 ML. High-resolution STM images indicated that asymmetric dimer rows always invert their phase in alternation with buckled dimer's up-end at the DVLs. Low-temperature STM images indicated that the symmetric dimer domains were due to flip-flopping of asymmetric dimers activated by large θ Ge at room temperature. The symmetric dimer domains extended along the dimer rows over the DVLs due to the phase correlation

Metal-porphyrin interactions. V. Kinetics of cyanide addition to a water soluble iron porphyrin dimer(1)

Energy Technology Data Exchange (ETDEWEB)

Hambright, P; Rishnamurthy, M K

1975-01-01

The kinetics of cyanide addition to the water-soluble oxybridged iron dimer of tetra (p-sulophenyl) porphin indicate that HCN is the reactant. The rate law is of the form: Rate = (3.8 +- 0.2) x 10/sup 4/ (Fe dimer) (HCN)/(1 + (3.1 +- 0.3) x 10/sup 10/ (H/sup +/)) at 25/sup 0/ ..mu.. = 0.7 (NaNO/sub 3/). The cyano iron dimer dissociates into dicyano iron monomers by two pathways, one first order in (H/sup +/), and one proportional to (H/sup +/)(CN/sup -/)/sup 2/. The mechanism of this dimer reaction is compared to iron porphyrin monomer systems.

Comparison of clinical probability-adjusted D-dimer and age-adjusted D-dimer interpretation to exclude venous thromboembolism.

Science.gov (United States)

Takach Lapner, Sarah; Julian, Jim A; Linkins, Lori-Ann; Bates, Shannon; Kearon, Clive

2017-10-05

Two new strategies for interpreting D-dimer results have been proposed: i) using a progressively higher D-dimer threshold with increasing age (age-adjusted strategy) and ii) using a D-dimer threshold in patients with low clinical probability that is twice the threshold used in patients with moderate clinical probability (clinical probability-adjusted strategy). Our objective was to compare the diagnostic accuracy of age-adjusted and clinical probability-adjusted D-dimer interpretation in patients with a low or moderate clinical probability of venous thromboembolism (VTE). We performed a retrospective analysis of clinical data and blood samples from two prospective studies. We compared the negative predictive value (NPV) for VTE, and the proportion of patients with a negative D-dimer result, using two D-dimer interpretation strategies: the age-adjusted strategy, which uses a progressively higher D-dimer threshold with increasing age over 50 years (age in years × 10 µg/L FEU); and the clinical probability-adjusted strategy which uses a D-dimer threshold of 1000 µg/L FEU in patients with low clinical probability and 500 µg/L FEU in patients with moderate clinical probability. A total of 1649 outpatients with low or moderate clinical probability for a first suspected deep vein thrombosis or pulmonary embolism were included. The NPV of both the clinical probability-adjusted strategy (99.7 %) and the age-adjusted strategy (99.6 %) were similar. However, the proportion of patients with a negative result was greater with the clinical probability-adjusted strategy (56.1 % vs, 50.9 %; difference 5.2 %; 95 % CI 3.5 % to 6.8 %). These findings suggest that clinical probability-adjusted D-dimer interpretation is a better way of interpreting D-dimer results compared to age-adjusted interpretation.

N-Annulated perylene-substituted and fused porphyrin dimers with intense near-infrared one-photon and two-photon absorption

KAUST Repository

Luo, Jie

2015-01-21

Fusion of two N-annulated perylene (NP) units with a fused porphyrin dimer along the S0-S1 electronic transition moment axis has resulted in new near-infrared (NIR) dyes 1a/1b with very intense absorption (ε>1.3×105M-1cm-1) beyond 1250nm. Both compounds displayed moderate NIR fluorescence with fluorescence quantum yields of 4.4×10-6 and 6.0×10-6 for 1a and 1b, respectively. The NP-substituted porphyrin dimers 2a/2b have also been obtained by controlled oxidative coupling and cyclodehydrogenation, and they showed superimposed absorptions of the fused porphyrin dimer and the NP chromophore. The excited-state dynamics of all of these compounds have been studied by femtosecond transient absorption measurements, which revealed porphyrin dimer-like behaviour. These new chromophores also exhibited good nonlinear optical susceptibility with large two-photon absorption cross-sections in the NIR region due to extended π-conjugation. Time-dependent density functional theory calculations have been performed to aid our understanding of their electronic structures and absorption spectra.

Local vibrational modes of the formic acid dimer - the strength of the double hydrogen bond

Science.gov (United States)

Kalescky, R.; Kraka, E.; Cremer, D.

2013-07-01

The 24 normal and 24 local vibrational modes of the formic acid dimer formed by two trans formic acid monomers to a ring (TT1) are analysed utilising preferentially experimental frequencies, but also CCSD(T)/CBS and ωB97X-D harmonic vibrational frequencies. The local hydrogen bond (HB) stretching frequencies are at 676 cm-1 and by this 482 and 412 cm-1 higher compared to the measured symmetric and asymmetric HB stretching frequencies at 264 and 194 cm-1. The adiabatic connection scheme between local and normal vibrational modes reveals that the lowering is due to the topology of dimer TT1, mass coupling, and avoided crossings involving the HṡṡṡOC bending modes. The HB local mode stretching force constant is related to the strength of the HB whereas the normal mode stretching force constant and frequency lead to an erroneous underestimation of the HB strength. The HB in TT1 is stabilised by electron delocalisation in the O=C-O units fostered by forming a ring via double HBs. This implies that the CO apart from the OH local stretching frequencies reflect the strength of the HB via their red or blue shifts relative to their corresponding values in trans formic acid.

Dimer self-organization of impurity ytterbium ions in synthetic forsterite single crystals

Science.gov (United States)

Tarasov, V. F.; Sukhanov, A. A.; Dudnikova, V. B.; Zharikov, E. V.; Lis, D. A.; Subbotin, K. A.

2017-07-01

Paramagnetic centers formed by impurity Yb3+ ions in synthetic forsterite (Mg2SiO4) grown by the Czochralski technique are studied by X-band CW and pulsed EPR spectroscopy. These centers are single ions substituting magnesium in two different crystallographic positions denoted M1 and M2, and dimer associates formed by two Yb3+ ions in nearby positions M1. It is established that there is a pronounced mechanism favoring self-organization of ytterbium ions in dimer associates during the crystal growth, and the mechanism of the spin-spin coupling between ytterbium ions in the associate has predominantly a dipole-dipole character, which makes it possible to control the energy of the spin-spin interaction by changing the orientation of the external magnetic field. The structural computer simulation of cluster ytterbium centers in forsterite crystals is carried out by the method of interatomic potentials using the GULP 4.0.1 code (General Utility Lattice Program). It is established that the formation of dimer associates in the form of a chain parallel to the crystallographic axis consisting of two ytterbium ions with a magnesium vacancy between them is the most energetically favorable for ytterbium ions substituting magnesium in the position M1.

Formic acid dimers in a nitrogen matrix

Science.gov (United States)

Lopes, Susy; Fausto, Rui; Khriachtchev, Leonid

2018-01-01

Formic acid (HCOOH) dimers are studied by infrared spectroscopy in a nitrogen matrix and by ab initio calculations. We benefit from the use of a nitrogen matrix where the lifetime of the higher-energy (cis) conformer is very long (˜11 h vs. 7 min in an argon matrix). As a result, in a nitrogen matrix, a large proportion of the cis conformer can be produced by vibrational excitation of the lower-energy (trans) conformer. Three trans-trans, four trans-cis, and three cis-cis dimers are found in the experiments. The spectroscopic information on most of these dimers is enriched compared to the previous studies in an argon matrix. The cis-cis dimers of ordinary formic acid (without deuteration) are reported here for the first time. Several conformational processes are obtained using selective excitation by infrared light, some of them also for the first time. In particular, we report on the formation of cis-cis dimers upon vibrational excitation of trans-cis dimers. Tunneling decays of several dimers have been detected in the dark. The tunneling decay of cis-cis dimers of formic acid as well as the stabilization of cis units in cis-cis dimers is also observed for the first time.

Procyanidin dimer B2-mediated IRAK-M induction negatively regulates TLR4 signaling in macrophages

Energy Technology Data Exchange (ETDEWEB)

Sung, Nak-Yun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Yang, Mi-So [Department of Microbiology, Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Song, Du-Sub [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); School of life sciences and Biotechnology, Korea University 5-ka, Anam-Dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of); Kim, Jae-Kyung; Park, Jong-Heum; Song, Beom-Seok; Park, Sang-Hyun; Lee, Ju-Woon [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Park, Hyun-Jin [School of life sciences and Biotechnology, Korea University 5-ka, Anam-Dong, Sungbuk-ku, Seoul 136-701 (Korea, Republic of); Kim, Jae-Hun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Baek, E-mail: ebbyun80@kaeri.re.kr [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Byun, Eui-Hong, E-mail: ehbyun80@kongju.ac.k [Department of Food Science and Technology, Kongju National University, Yesan 340-800 (Korea, Republic of)

2013-08-16

Highlights: •Pro B2 elevated the expression of IRAK-M, a negative regulator of TLR signaling. •LPS-induced expression of cell surface molecules was inhibited by Pro B2. •LPS-induced production of pro-inflammatory cytokines was inhibited by Pro B2. •Pro B2 inhibited LPS-induced activation of MAPKs and NF-κB through IRAK-M. •Pro B2 inactivated naïve T cells by inhibiting LPS-induced cytokines via IRAK-M. -- Abstract: Polyphenolic compounds have been found to possess a wide range of physiological activities that may contribute to their beneficial effects against inflammation-related diseases; however, the molecular mechanisms underlying this anti-inflammatory activity are not completely characterized, and many features remain to be elucidated. In this study, we investigated the molecular basis for the down-regulation of toll-like receptor 4 (TLR4) signal transduction by procyanidin dimer B2 (Pro B2) in macrophages. Pro B2 markedly elevated the expression of the interleukin (IL)-1 receptor-associated kinase (IRAK)-M protein, a negative regulator of TLR signaling. Lipopolysaccharide (LPS)-induced expression of cell surface molecules (CD80, CD86, and MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis factor-α, IL-1β, IL-6, and IL-12p70) were inhibited by Pro B2, and this action was prevented by IRAK-M silencing. In addition, Pro B2-treated macrophages inhibited LPS-induced activation of mitogen-activated protein kinases such as extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase and the translocation of nuclear factor κB and p65 through IRAK-M. We also found that Pro B2-treated macrophages inactivated naïve T cells by inhibiting LPS-induced interferon-γ and IL-2 secretion through IRAK-M. These novel findings provide new insights into the understanding of negative regulatory mechanisms of the TLR4 signaling pathway and the immune-pharmacological role of Pro B2 in the immune response against the development

A study of the dimer formation of Rous sarcoma virus RNA and of its effect on viral protein synthesis in vitro.

Science.gov (United States)

Bieth, E; Gabus, C; Darlix, J L

1990-01-11

The genetic material of all retroviruses examined so far is an RNA dimer where two identical RNA subunits are joined at their 5' ends by a structure named dimer linkage structure (DLS). Since the precise location and structure of the DLS as well as the mechanism and role(s) of RNA dimerization remain unclear, we analysed the dimerization process of Rous sarcoma virus (RSV) RNA. For this purpose we set up an in vitro model for RSV RNA dimerization. Using this model RSV RNA was shown to form dimeric molecules and this dimerization process was greatly activated by nucleocapsid protein (NCp12) of RSV. Furthermore, RSV RNA dimerization was performed in the presence of complementary 5'32P-DNA oligomers in order to probe the monomer and dimer forms of RSV RNA. Data indicated that the DLS of RSV RNA probably maps between positions 544-564 from the 5' end. In an attempt to define sequences needed for the dimerization of RSV RNA, deletion mutageneses were generated in the 5' 600 nt. The results showed that the dimer promoting sequences probably are located within positions 208-270 and 400-600 from the 5' end and hence possibly encompassing the cis-acting elements needed for the specific encapsidation of RSV genomic RNA. Also it is reported that synthesis of the polyprotein precursor Pr76gag is inhibited upon dimerization of RSV RNA. These results suggest that dimerization and encapsidation of genome length RSV RNA might be linked in the course of virion formation since they appear to be under the control of the same cis elements, E and DLS, and the trans-acting factor nucleocapsid protein NCp12.

Elucidation of cladofulvin biosynthesis reveals a cytochrome P450 monooxygenase required for anthraquinone dimerization.

Science.gov (United States)

Griffiths, Scott; Mesarich, Carl H; Saccomanno, Benedetta; Vaisberg, Abraham; De Wit, Pierre J G M; Cox, Russell; Collemare, Jérôme

2016-06-21

Anthraquinones are a large family of secondary metabolites (SMs) that are extensively studied for their diverse biological activities. These activities are determined by functional group decorations and the formation of dimers from anthraquinone monomers. Despite their numerous medicinal qualities, very few anthraquinone biosynthetic pathways have been elucidated so far, including the enzymatic dimerization steps. In this study, we report the elucidation of the biosynthesis of cladofulvin, an asymmetrical homodimer of nataloe-emodin produced by the fungus Cladosporium fulvum A gene cluster of 10 genes controls cladofulvin biosynthesis, which begins with the production of atrochrysone carboxylic acid by the polyketide synthase ClaG and the β-lactamase ClaF. This compound is decarboxylated by ClaH to yield emodin, which is then converted to chrysophanol hydroquinone by the reductase ClaC and the dehydratase ClaB. We show that the predicted cytochrome P450 ClaM catalyzes the dimerization of nataloe-emodin to cladofulvin. Remarkably, such dimerization dramatically increases nataloe-emodin cytotoxicity against mammalian cell lines. These findings shed light on the enzymatic mechanisms involved in anthraquinone dimerization. Future characterization of the ClaM enzyme should facilitate engineering the biosynthesis of novel, potent, dimeric anthraquinones and structurally related compound families.

Structure–Activity Relationship of Oligomeric Flavan-3-ols: Importance of the Upper-Unit B-ring Hydroxyl Groups in the Dimeric Structure for Strong Activities

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Yoshitomo Hamada

2015-10-01

Full Text Available Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4–8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (−-epigallocatechin-[4,8]-(+-catechin, (−-epigallocatechin-[4,8]-(−-epigallocatechin, (−-epigallocatechin-[4,8]-(−-epigallocatechin-3-O-gallate, and (+-catechin-[4,8]-(−-epigallocatechin and performed structure–activity relationship (SAR studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity.

High-resolution Crystal Structure of Dimeric VP40 From Sudan ebolavirus.

Science.gov (United States)

Clifton, Matthew C; Bruhn, Jessica F; Atkins, Kateri; Webb, Terry L; Baydo, Ruth O; Raymond, Amy; Lorimer, Donald D; Edwards, Thomas E; Myler, Peter J; Saphire, Erica Ollmann

2015-10-01

Ebolaviruses cause severe hemorrhagic fever. Central to the Ebola life cycle is the matrix protein VP40, which oligomerizes and drives viral budding. Here we present the crystal structure of the Sudan virus (SUDV) matrix protein. This structure is higher resolution (1.6 Å) than previously achievable. Despite differences in the protein purification, we find that it still forms a stable dimer in solution, as was noted for other Ebola VP40s. Although the N-terminal domain interface by which VP40 dimerizes is conserved between Ebola virus and SUDV, the C-terminal domain interface by which VP40 dimers may further assemble is significantly smaller in this SUDV assembly. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

D-dimers (DD) in CVST.

Science.gov (United States)

Wang, Hui Fang; Pu, Chuan Qiang; Yin, Xi; Tian, Cheng Lin; Chen, Ting; Guo, Jun Hong; Shi, Qiang

2017-06-01

We were interested in further confirming whether D-dimers (DD) are indeed elevated in cerebral venous sinus thrombosis (CVST) as reported in those studies. CVST patients who had a plasma D-dimer test (139 cases) were included and divided into two groups: elevated D-dimer group (EDG) (>0.5 μg/mL; 65 cases) and normal D-dimer group (NDG) (≤0.5 μg/mL; 74 cases). The two groups were compared in terms of demographic data, clinical manifestation, laboratory and imaging data, using inferential statistical methods. The chi-squared and Fisher exact test showed that, compared to the NDG (74 cases), patients with elevated D-dimer levels were more likely to have a shorter symptom duration (SD) (30 ± 83.9 versus 90 ± 58.9 d, p = 0.003), more risk factors (75.4% versus 52.7%, p = 0.006), higher multiple venous sinus involvement (75.4% versus 59.5%, p = 0.037), increased fibrinogen (43.1% versus 18.9%, p = 0.037) and higher levels of blood glucose (18.3% versus 11%, p = 0.037). According to correlation analyses, D-dimer levels were positively correlated with number of venous sinuses involvement (NVS) (r = 0.321, p = 0.009) in the EDG. Multivariate logistic regression analysis showed that SD (OR, 0.025; 95% CI, 1.324-6.043; p = 0.000), NVS (OR, 1.573; 95% CI, 1.15-2.151; p = 0.005) and risk factors (OR, 3.321; 95% CI, 1.451-7.564; p = 0.004) were significantly different between the two groups. D-dimer is elevated in patients with acute/subacute CVST.

Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

International Nuclear Information System (INIS)

Masek, F.; Sedliakova, M.

1978-01-01

The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm 2 and at different time intervals with a second fluence of 500 ergs/mm 2 . After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr + and E.coli 15 555-7, but not in E.coli K12 SR20. (author)

Involvement of UV-inducible repair in pyrimidine dimer excision in Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Masek, F; Sedliakova, M [Slovenska Akademia Vied, Bratislava (Czechoslovakia)

1978-11-15

The influence of UV radiation on pyrimidine dimer excision in the cells of three excision-proficient E.coli strains was studied. For this purpose cells were irradiated with a first fluence of 300 ergs/mm/sup 2/ and at different time intervals with a second fluence of 500 ergs/mm/sup 2/. After the second fluence dimer excision was found to be partly inhibited in E.coli B/r Hcr/sup +/ and E.coli 15 555-7, but not in E.coli K12 SR20.

Study of structural stability and damaging effect on membrane for four Aβ42 dimers.

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Wei Feng

Full Text Available Increasing evidence shows that Aβ oligomers are key pathogenic molecules in Alzheimer's disease. Among Aβ oligomers, dimer is the smallest aggregate and toxic unit. Therefore, understanding its structural and dynamic properties is quite useful to prevent the formation and toxicity of the Aβ oligomers. In this study, we performed molecular dynamic simulations on four Aβ42 dimers, 2NCb, CNNC, NCNC and NCCN, within the hydrated DPPC membrane. Four Aβ42 dimers differ in the arrangements of two Aβ42 peptides. This study aims to investigate the impact of aggregation pattern of two Aβ peptides on the structural stability of the Aβ42 dimer and its disruption to the biological membrane. The MD results demonstrate that the NCCN, CNNC and NCNC have the larger structural fluctuation at the N-terminus of Aβ42 peptide, where the β-strand structure converts into the coil structure. The loss of the N-terminal β-strand further impairs the aggregate ability of Aβ42 dimer. In addition, inserting Aβ42 dimer into the membrane can considerably decrease the average APL of DPPC membrane. Moreover this decrease effect is largely dependent on the distance to the location of Aβ42 dimer and its secondary structure forms. Based on the results, the 2NCb is considered as a stable dimeric unit for aggregating the larger Aβ42 oligomer, and has a potent ability to disrupt the membrane.

Species A rotavirus NSP3 acquires its translation inhibitory function prior to stable dimer formation.

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Hugo I Contreras-Treviño

Full Text Available Species A rotavirus non-structural protein 3 (NSP3 is a translational regulator that inhibits or, under some conditions, enhances host cell translation. NSP3 binds to the translation initiation factor eIF4G1 and evicts poly-(A binding protein (PABP from eIF4G1, thus inhibiting translation of polyadenylated mRNAs, presumably by disrupting the effect of PABP bound to their 3'-ends. NSP3 has a long coiled-coil region involved in dimerization that includes a chaperone Hsp90-binding domain (HS90BD. We aimed to study the role in NSP3 dimerization of a segment of the coiled-coil region adjoining the HS90BD. We used a vaccinia virus system to express NSP3 with point mutations in conserved amino acids in the coiled-coil region and determined the effects of these mutations on translation by metabolic labeling of proteins as well as on accumulation of stable NSP3 dimers by non-dissociating Western blot, a method that separates stable NSP3 dimers from the monomer/dimerization intermediate forms of the protein. Four of five mutations reduced the total yield of NSP3 and the formation of stable dimers (W170A, K171E, R173E and R187E:K191E, whereas one mutation had the opposite effects (Y192A. Treatment with the proteasome inhibitor MG132 revealed that stable NSP3 dimers and monomers/dimerization intermediates are susceptible to proteasome degradation. Surprisingly, mutants severely impaired in the formation of stable dimers were still able to inhibit host cell translation, suggesting that NSP3 dimerization intermediates are functional. Our results demonstrate that rotavirus NSP3 acquires its function prior to stable dimer formation and remain as a proteasome target throughout dimerization.

Structure of the dimeric N-glycosylated form of fungal β-N-acetylhexosaminidase revealed by computer modeling, vibrational spectroscopy, and biochemical studies

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Sklenář Jan

2007-05-01

Full Text Available Abstract Background Fungal β-N-acetylhexosaminidases catalyze the hydrolysis of chitobiose into its constituent monosaccharides. These enzymes are physiologically important during the life cycle of the fungus for the formation of septa, germ tubes and fruit-bodies. Crystal structures are known for two monomeric bacterial enzymes and the dimeric human lysosomal β-N-acetylhexosaminidase. The fungal β-N-acetylhexosaminidases are robust enzymes commonly used in chemoenzymatic syntheses of oligosaccharides. The enzyme from Aspergillus oryzae was purified and its sequence was determined. Results The complete primary structure of the fungal β-N-acetylhexosaminidase from Aspergillus oryzae CCF1066 was used to construct molecular models of the catalytic subunit of the enzyme, the enzyme dimer, and the N-glycosylated dimer. Experimental data were obtained from infrared and Raman spectroscopy, and biochemical studies of the native and deglycosylated enzyme, and are in good agreement with the models. Enzyme deglycosylated under native conditions displays identical kinetic parameters but is significantly less stable in acidic conditions, consistent with model predictions. The molecular model of the deglycosylated enzyme was solvated and a molecular dynamics simulation was run over 20 ns. The molecular model is able to bind the natural substrate – chitobiose with a stable value of binding energy during the molecular dynamics simulation. Conclusion Whereas the intracellular bacterial β-N-acetylhexosaminidases are monomeric, the extracellular secreted enzymes of fungi and humans occur as dimers. Dimerization of the fungal β-N-acetylhexosaminidase appears to be a reversible process that is strictly pH dependent. Oligosaccharide moieties may also participate in the dimerization process that might represent a unique feature of the exclusively extracellular enzymes. Deglycosylation had only limited effect on enzyme activity, but it significantly affected

Molecular recognition of epothilones by microtubules and tubulin dimers revealed by biochemical and NMR approaches.

Science.gov (United States)

Canales, Angeles; Nieto, Lidia; Rodríguez-Salarichs, Javier; Sánchez-Murcia, Pedro A; Coderch, Claire; Cortés-Cabrera, Alvaro; Paterson, Ian; Carlomagno, Teresa; Gago, Federico; Andreu, José M; Altmann, Karl-Heinz; Jiménez-Barbero, Jesús; Díaz, J Fernando

2014-04-18

The binding of epothilones to dimeric tubulin and to microtubules has been studied by means of biochemical and NMR techniques. We have determined the binding constants of epothilone A (EpoA) and B (EpoB) to dimeric tubulin, which are 4 orders of magnitude lower than those for microtubules, and we have elucidated the conformation and binding epitopes of EpoA and EpoB when bound to tubulin dimers and microtubules in solution. The determined conformation of epothilones when bound to dimeric tubulin is similar to that found by X-ray crystallographic techniques for the binding of EpoA to the Tubulin/RB3/TTL complex; it is markedly different from that reported for EpoA bound to zinc-induced sheets obtained by electron crystallography. Likewise, only the X-ray structure of EpoA bound to the Tubulin/RB3/TTL complex at the luminal site, but not the electron crystallography structure, is compatible with the results obtained by STD on the binding epitope of EpoA bound to dimeric tubulin, thus confirming that the allosteric change (structuring of the M-loop) is the biochemical mechanism of induction of tubulin assembly by epothilones. TR-NOESY signals of EpoA bound to microtubules have been obtained, supporting the interaction with a transient binding site with a fast exchange rate (pore site), consistent with the notion that epothilones access the luminal site through the pore site, as has also been observed for taxanes. Finally, the differences in the tubulin binding affinities of a series of epothilone analogues has been quantitatively explained using the newly determined binding pose and the COMBINE methodology.

Dimerization of BTas is required for the transactivational activity of bovine foamy virus

International Nuclear Information System (INIS)

Tan Juan; Qiao Wentao; Xu Fengwen; Han Hongqi; Chen Qimin; Geng Yunqi

2008-01-01

The BTas protein of bovine foamy virus (BFV) is a 249-amino-acid nuclear regulatory protein which transactivates viral gene expression directed by the long terminal repeat promoter (LTR) and the internal promoter (IP). Here, we demonstrate the BTas protein forms a dimeric complex in mammalian cells by using mammalian two hybrid systems and cross-linking assay. Functional analyses with deletion mutants reveal that the region of 46-62aa is essential for dimer formation. Furthermore, our results show that deleting the dimerization region of BTas did not affect the localization of BTas, but that it did result in the loss of its transactivational activity on the LTR and IP. Furthermore, BTas (Δ46-62aa) retained binding ability to the LTR and IP similar to that of the wild-type BTas. These data suggest the dimerization region is necessary for the transactivational function of BTas and is crucial to the replication of BFV

Model-Based Comparison of Antibody Dimerization in Continuous and Batch-Wise Downstream Processing

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Anton Sellberg

2015-07-01

Full Text Available Monoclonal antibodies are generally produced using a generic platform approach in which several chromatographic separations assure high purity of the product. Dimerization can occur during the fermentation stage and may occur also during the downstream processing. We present here simulations in which a traditional platform approach that consist of protein A capture, followed by cation-exchange and anion-exchange chromatography for polishing is compared to a continuous platform in which dimer removal and virus inactivation are carried out on a size-exclusion column. A dimerization model that takes pH, salt concentration and the concentration of antibodies into account is combined with chromatographic models, to be able to predicted both the separation and the degree to which dimers are formed. Purification of a feed composition that contained 1% by weight of dimer and a total antibody concentration of 1 g/L was modeled using both approaches, and the amount of antibodies in the continuous platform was at least 4 times lower than in the traditional platform. The total processing time was also lower, as the cation-exchange polish could be omitted.

A redox-dependent dimerization switch regulates activity and tolerance for reactive oxygen species of barley seed glutathione peroxidase

DEFF Research Database (Denmark)

Navrot, Nicolas; Skjoldager, Nicklas; Bunkenborg, Jakob

2015-01-01

Monomeric and dimeric forms of recombinant barley (Hordeum vulgare subsp. vulgare) glutathione peroxidase 2 (HvGpx2) are demonstrated to display distinctly different functional properties in vitro. Monomeric HvGpx2 thus has five fold higher catalytic efficiency than the dimer towards tert-butyl h...

Structures and energetics of lithium adatom and its dimer on graphene–a DFT study

International Nuclear Information System (INIS)

Kaur, Gagandeep; Gupta, Shuchi; Dharamvir, Keya

2015-01-01

Highlights: • For single Li adatom adsorption on graphene, it prefers H-site followed by B-site. • By the examination of the calculated cohesive energies, it is possible to conclude that both Li/Li 2 binds strongly to graphene which corroborate previous results. • The calculations showed that the interaction between Li and graphene has minimal effects on the electronic states of the graphene sheet, in agreement with previous calculations. • Charge transfer (0.338e)upon adsorption also induces significant electric dipole moments and affect total magnetic moment at B-site and T-site. • For the Li dimer adsorption, we found that horizontal orientation is favored over the vertical. • Adsorption of lithium dimer to the HH-site alters graphene sheet only by small amount ∼0.0022 Å–0.0034 Å. • The methodology demonstrated in this paper maybe applied to larger lithium clusters on graphene sheet. - Abstract: We performed a systematic density functional theory (DFT) study of the adsorption of Lithium adatom and its dimer on graphene using SIESTA package [1], in the generalized gradient approximation (GGA). The adsorption energy, geometry, charge transfer and density of states of adatom/dimer-graphene system are calculated. The calculations showed that the interaction between Li adatom and graphene is strong (∼1.07 eV) and it prefers to adsorb on H-site. Further calculations of both horizontally and vertically aligned dimers show that the adsorption is also weak for the latter orientation. The preferred orientation of each dimer was found to be parallel to graphene sheet with the two atoms of the dimer occupying adjacent H-sites on the graphene. Significant charge transfer (∼0.388e) from Li adatom to graphene will induce electric dipole moments in the adatom/graphene system. We also calculated DOS for the stable Li -graphene system. The Fermi energy is seen to lie above the Dirac point inside the conduction band indicating that appreciable electrons

The dimerization of thiophosgene and trichlorothioacetyl chloride S-imides - Head-to-head and/or head-to-tail?

DEFF Research Database (Denmark)

Voss, Jürgen; Buddensiek, Dirk; Senning, Alexander Erich Eugen

2016-01-01

It has been shown that certain N-aryltrichoromethanesulfenamides Cl3C-S-NHAr can be dehydrochlorinated to form red-colored thiocarbonyl S-imides CCl2=S=NAr which dimerize spontaneously. The dimers so far obtained were first assigned the 1,4,2,5-dithiadiazinane structure but later shown to be the ...

Dimer formation and transcription activation in the sporulation response regulator Spo0A.

Science.gov (United States)

Lewis, Richard J; Scott, David J; Brannigan, James A; Ladds, Joanne C; Cervin, Marguerite A; Spiegelman, George B; Hoggett, James G; Barák, Imrich; Wilkinson, Anthony J

2002-02-15

The response regulator Spo0A is the master control element in the initiation of sporulation in Bacillus subtilis. Like many other multi-domain response regulators, the latent activity of the effector, C-terminal domain is stimulated by phosphorylation on a conserved aspartic acid residue in the regulatory, N-terminal domain. If a threshold concentration of phosphorylated Spo0A is achieved, the transcription of genes required for sporulation is activated, whereas the genes encoding stationary phase sentinels are repressed, and sporulation proceeds. Despite detailed genetic, biochemical and structural characterisation, it is not understood how the phosphorylation signal in the receiver domain is transduced into DNA binding and transcription activation in the distal effector domain. An obstacle to our understanding of Spo0A function is the uncertainty concerning changes in quaternary structure that accompany phosphorylation. Here we have revisited this question and shown unequivocally that Spo0A forms dimers upon phosphorylation and that the subunit interactions in the dimer are mediated principally by the receiver domain. Purified dimers of two mutants of Spo0A, in which the phosphorylatable aspartic acid residue has been substituted, activate transcription from the spoIIG promoter in vitro, whereas monomers do not. This suggests that dimers represent the activated form of Spo0A. Copyright 2002 Elsevier Science Ltd.

Van der Waals potential and vibrational energy levels of the ground state radon dimer

Science.gov (United States)

Sheng, Xiaowei; Qian, Shifeng; Hu, Fengfei

2017-08-01

In the present paper, the ground state van der Waals potential of the Radon dimer is described by the Tang-Toennies potential model, which requires five essential parameters. Among them, the two dispersion coefficients C6 and C8 are estimated from the well determined dispersion coefficients C6 and C8 of Xe2. C10 is estimated by using the approximation equation that C6C10/C82 has an average value of 1.221 for all the rare gas dimers. With these estimated dispersion coefficients and the well determined well depth De and Re the Born-Mayer parameters A and b are derived. Then the vibrational energy levels of the ground state radon dimer are calculated. 40 vibrational energy levels are observed in the ground state of Rn2 dimer. The last vibrational energy level is bound by only 0.0012 cm-1.

Repair of closely opposed cyclobutyl pyrimidine dimers in UV-sensitive human diploid fibroblasts

International Nuclear Information System (INIS)

Lam, L.H.; Reynolds, R.J.

1986-01-01

An enzyme-sensitive site assay has been used to examine the fate of closely opposed pyrimidine dimers in fibroblasts from individuals afflicted with various genetic disorders that confer increased cellular sensitivity to UV radiation. The disappearance of bifilar enzyme-sensitive sites was found to be normal in cells from individuals with Fanconi's anemia, Cockayne's syndrome, dyskeratosis congenita and the variant form of xeroderma pigmentosum. The rate of bifilar enzyme-sensitive site removal in XP cells assigned to complementation group C was reduced by an amount similar to that observed for the repair of isolated dimers. Our results indicate that the initiation of repair at closely opposed dimers is slow in XP-C cells but normal in all other cells examined. (Auth.)

Structural and dynamic studies of the dimerization and DNA-binding domains of the transcription factors v-Myc and Max

International Nuclear Information System (INIS)

Fieber, W.

2001-05-01

In the present work, solution structural and dynamic properties of the dimerization and DNA binding domains of the transcription factors v-Myc and Max were characterized by NMR and CD spectroscopy. It could be demonstrated that v-Myc in the absence of its authentic binding partner Max does not homodimerize, but exists in a monomeric and prestructured form. Two separated α-helical regions in the leucine zipper region and in the basic-H1 region, respectively, could be identified, while the latter appeared to be less stable. Both helices lack stabilizing tertiary side chain interactions and represent exceptional examples for loosely coupled, structured segments in a native protein. The structure of v-Myc is dynamic and can be described as a distribution of conformational substates. Motion within the substates comprise fast (picosecond to nanosecond) local backbone fluctuations like helical fraying, whereas motion between the substates comprise the relative orientation of the two helices and occur at larger time scales (microsecond to millisecond). The preformation of the specific protein and DNA binding sites, leucine zipper and the basic region, presumably allows rapid and accurate recognition of the respective binding partners. v-Myc-Max and Max-Max protein preparations were shown to form stable dimers. Thermodynamic analysis of the dissociation reactions of v-Myc-Max revealed a significant higher stability of the heterodimer than of the Max-Max homodimer over the whole temperature range. It could be demonstrated that the restricted conformational space of the v-Myc bHLHZip domain reduces the entropy penalty associated with dimerization and contributes to the preference of Max to form heterodimers with v-Myc rather than homodimers. (author)

Structural basis for TatA oligomerization: an NMR study of Escherichia coli TatA dimeric structure.

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Yi Zhang

Full Text Available Many proteins are transported across lipid membranes by protein translocation systems in living cells. The twin-arginine transport (Tat system identified in bacteria and plant chloroplasts is a unique system that transports proteins across membranes in their fully-folded states. Up to date, the detailed molecular mechanism of this process remains largely unclear. The Escherichia coli Tat system consists of three essential transmembrane proteins: TatA, TatB and TatC. Among them, TatB and TatC form a tight complex and function in substrate recognition. The major component TatA contains a single transmembrane helix followed by an amphipathic helix, and is suggested to form the translocation pore via self-oligomerization. Since the TatA oligomer has to accommodate substrate proteins of various sizes and shapes, the process of its assembly stands essential for understanding the translocation mechanism. A structure model of TatA oligomer was recently proposed based on NMR and EPR observations, revealing contacts between the transmembrane helices from adjacent subunits. Herein we report the construction and stabilization of a dimeric TatA, as well as the structure determination by solution NMR spectroscopy. In addition to more extensive inter-subunit contacts between the transmembrane helices, we were also able to observe interactions between neighbouring amphipathic helices. The side-by-side packing of the amphipathic helices extends the solvent-exposed hydrophilic surface of the protein, which might be favourable for interactions with substrate proteins. The dimeric TatA structure offers more detailed information of TatA oligomeric interface and provides new insights on Tat translocation mechanism.

Investigation of the hydrated 7-hydroxy-4-methylcoumarin dimer by combined IR/UV spectroscopy

International Nuclear Information System (INIS)

Stamm, A.; Schwing, K.; Gerhards, M.

2014-01-01

The first molecular beam investigations on a coumarin dimer and clusters of a coumarin dimer with water both in the neutral (S 0 ) and cationic (D 0 ) electronic ground state are performed. The structure and structural changes due to ionization of the isolated 7-hydroxy-4-methylcoumarin dimer (7H4MC) 2 as well as its mono- and dihydrate (7H4MC) 2 (H 2 O) 1-2 are analyzed by applying combined IR/UV spectroscopy compared with density functional theory calculations. In case of the neutral dimer of 7H4MC a doubly hydrogen-bonded structure is formed. This doubly hydrogen-bonded arrangement opens to a singly hydrogen-bonded structure in the ion presenting a rearrangement reaction within an isolated dimer. By attaching one or two water molecules to the neutral 7H4MC dimer water is inserted into the hydrogen bonds. In contrast to the non-hydrated species this general binding motif with water in a bridging function does not change via ionization but especially for the dihydrate the spatial arrangement of the two 7H4MC units changes strengthening the interaction between the aromatic chromophores. The presented analyses illustrate the strong dependence of binding motifs as a function of successive hydration and charge including a rearrangement reaction

Stochastic optimization-based study of dimerization kinetics

Indian Academy of Sciences (India)

To this end, we study dimerization kinetics of protein as a model system. We follow the dimerization kinetics using a stochastic simulation algorithm and ... optimization; dimerization kinetics; sensitivity analysis; stochastic simulation ... tion in large molecules and clusters, or the design ..... An unbiased strategy of allocating.

High-speed atomic force microscopy reveals structural dynamics of α -synuclein monomers and dimers

Science.gov (United States)

Zhang, Yuliang; Hashemi, Mohtadin; Lv, Zhengjian; Williams, Benfeard; Popov, Konstantin I.; Dokholyan, Nikolay V.; Lyubchenko, Yuri L.

2018-03-01

α-Synuclein (α-syn) is the major component of the intraneuronal inclusions called Lewy bodies, which are the pathological hallmark of Parkinson's disease. α-Syn is capable of self-assembly into many different species, such as soluble oligomers and fibrils. Even though attempts to resolve the structures of the protein have been made, detailed understanding about the structures and their relationship with the different aggregation steps is lacking, which is of interest to provide insights into the pathogenic mechanism of Parkinson's disease. Here we report the structural flexibility of α-syn monomers and dimers in an aqueous solution environment as probed by single-molecule time-lapse high-speed AFM. In addition, we present the molecular basis for the structural transitions using discrete molecular dynamics (DMD) simulations. α-Syn monomers assume a globular conformation, which is capable of forming tail-like protrusions over dozens of seconds. Importantly, a globular monomer can adopt fully extended conformations. Dimers, on the other hand, are less dynamic and show a dumbbell conformation that experiences morphological changes over time. DMD simulations revealed that the α-syn monomer consists of several tightly packed small helices. The tail-like protrusions are also helical with a small β-sheet, acting as a "hinge". Monomers within dimers have a large interfacial interaction area and are stabilized by interactions in the non-amyloid central (NAC) regions. Furthermore, the dimer NAC-region of each α-syn monomer forms a β-rich segment. Moreover, NAC-regions are located in the hydrophobic core of the dimer.

Retroviral RNA Dimerization: From Structure to Functions

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Noé Dubois

2018-03-01

Full Text Available The genome of the retroviruses is a dimer composed by two homologous copies of genomic RNA (gRNA molecules of positive polarity. The dimerization process allows two gRNA molecules to be non-covalently linked together through intermolecular base-pairing. This step is critical for the viral life cycle and is highly conserved among retroviruses with the exception of spumaretroviruses. Furthermore, packaging of two gRNA copies into viral particles presents an important evolutionary advantage for immune system evasion and drug resistance. Recent studies reported RNA switches models regulating not only gRNA dimerization, but also translation and packaging, and a spatio-temporal characterization of viral gRNA dimerization within cells are now at hand. This review summarizes our current understanding on the structural features of the dimerization signals for a variety of retroviruses (HIVs, MLV, RSV, BLV, MMTV, MPMV…, the mechanisms of RNA dimer formation and functional implications in the retroviral cycle.

Aromatic C-Nitroso Compounds and Their Dimers: A Model for Probing the Reaction Mechanisms in Crystalline Molecular Solids

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Ivana Biljan

2017-12-01

Full Text Available This review is focused on the dimerization and dissociation of aromatic C-nitroso compounds and their dimers, the reactions that could be used as a convenient model for studying the thermal organic solid-state reaction mechanisms. This molecular model is simple because it includes formation or breaking of only one covalent bond between two nitrogen atoms. The crystalline molecular solids of nitroso dimers (azodioxides dissociate by photolysis under the cryogenic conditions, and re-dimerize by slow warming. The thermal re-dimerization reaction is examined under the different topotactic conditions in crystals: disordering, surface defects, and phase transformations. Depending on the conditions, and on the molecular structure, aromatic C-nitroso compounds can associate to form one-dimensional polymeric structures and are able to self-assemble on gold surfaces.

Fluorescence Microspectroscopy for Testing the Dimerization Hypothesis of BACE1 Protein in Cultured HEK293 Cells

Science.gov (United States)

Gardeen, Spencer; Johnson, Joseph L.; Heikal, Ahmed A.

2016-06-01

Alzheimer's Disease (AD) is a neurodegenerative disorder that results from the formation of beta-amyloid plaques in the brain that trigger the known symptoms of memory loss in AD patients. The beta-amyloid plaques are formed by the proteolytic cleavage of the amyloid precursor protein (APP) by the proteases BACE1 and gamma-secretase. These enzyme-facilitated cleavages lead to the production of beta-amyloid fragments that aggregate to form plaques, which ultimately lead to neuronal cell death. Recent detergent protein extraction studies suggest that BACE1 protein forms a dimer that has significantly higher catalytic activity than its monomeric counterpart. In this contribution, we examine the dimerization hypothesis of BACE1 in cultured HEK293 cells using complementary fluorescence spectroscopy and microscopy methods. Cells were transfected with a BACE1-EGFP fusion protein construct and imaged using confocal, and differential interference contrast to monitor the localization and distribution of intracellular BACE1. Complementary fluorescence lifetime and anisotropy measurements enabled us to examine the conformational and environmental changes of BACE1 as a function of substrate binding. Using fluorescence correlation spectroscopy, we also quantified the diffusion coefficient of BACE1-EGFP on the plasma membrane as a means to test the dimerization hypothesis as a fucntion of substrate-analog inhibitition. Our results represent an important first towards examining the substrate-mediated dimerization hypothesis of BACE1 in live cells.

Statistical transmutation in doped quantum dimer models.

Science.gov (United States)

Lamas, C A; Ralko, A; Cabra, D C; Poilblanc, D; Pujol, P

2012-07-06

We prove a "statistical transmutation" symmetry of doped quantum dimer models on the square, triangular, and kagome lattices: the energy spectrum is invariant under a simultaneous change of statistics (i.e., bosonic into fermionic or vice versa) of the holes and of the signs of all the dimer resonance loops. This exact transformation enables us to define the duality equivalence between doped quantum dimer Hamiltonians and provides the analytic framework to analyze dynamical statistical transmutations. We investigate numerically the doping of the triangular quantum dimer model with special focus on the topological Z(2) dimer liquid. Doping leads to four (instead of two for the square lattice) inequivalent families of Hamiltonians. Competition between phase separation, superfluidity, supersolidity, and fermionic phases is investigated in the four families.

Strain mediated interaction of adatom dimers

OpenAIRE

Kappus, Wolfgang

2013-01-01

An earlier model for substrate strain mediated interactions between monomer adatoms is extended to the interaction of monomers with dimers and the interaction of dimers. While monomers (sitting on high symmetric sites) are supposed to create isotropic stress on the substrate, dimers would create anisotropic stress caused by stretching their bond. Resulting interactions are strongly angle dependent and also reflect the elastic anisotropy of the substrate. The applicability of a continuum elast...

The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: crystal structure and biological functions.

Science.gov (United States)

Tochowicz, Anna; Goettig, Peter; Evans, Richard; Visse, Robert; Shitomi, Yasuyuki; Palmisano, Ralf; Ito, Noriko; Richter, Klaus; Maskos, Klaus; Franke, Daniel; Svergun, Dmitri; Nagase, Hideaki; Bode, Wolfram; Itoh, Yoshifumi

2011-03-04

Homodimerization is an essential step for membrane type 1 matrix metalloproteinase (MT1-MMP) to activate proMMP-2 and to degrade collagen on the cell surface. To uncover the molecular basis of the hemopexin (Hpx) domain-driven dimerization of MT1-MMP, a crystal structure of the Hpx domain was solved at 1.7 Å resolution. Two interactions were identified as potential biological dimer interfaces in the crystal structure, and mutagenesis studies revealed that the biological dimer possesses a symmetrical interaction where blades II and III of molecule A interact with blades III and II of molecule B. The mutations of amino acids involved in the interaction weakened the dimer interaction of Hpx domains in solution, and incorporation of these mutations into the full-length enzyme significantly inhibited dimer-dependent functions on the cell surface, including proMMP-2 activation, collagen degradation, and invasion into the three-dimensional collagen matrix, whereas dimer-independent functions, including gelatin film degradation and two-dimensional cell migration, were not affected. These results shed light on the structural basis of MT1-MMP dimerization that is crucial to promote cellular invasion.

Diatomic substitutionals in superconducting Nb(1-x)B2

International Nuclear Information System (INIS)

Farrell, H.H.; LaViolette, Randall A.; Lillo, T.M.

2006-01-01

Using first-principles, density functional theory calculations, we have shown that the increase in superconducting critical temperature to above 9 K experimentally observed for B-rich, off-stoichiometry NbB 2 material is associated with the formation of B-dimers on Nb sites rather than with the formation of Nb vacancies, as previously proposed. Our calculations show that certain of these B-dimer configurations have lower binding energies than do the vacancy structures. This result is pressure independent in the range between 0 and 10 GPa, and above. Further, the dimer-containing materials have a higher electronic density of states at the Fermi level than do the vacancy structures. Finally, the presence of B-dimers results in the splitting off of phonon normal modes. These last two factors are relevant to the improved superconducting properties

Formation of pyrimidine dimers in Simian virus 40 chromosomes and DNA in vitro: effects of salt

International Nuclear Information System (INIS)

Edenberg, H.J.

1984-01-01

Simian virus 40 chromosomes were used to determine whether packaging of DNA into chromatin affected the yield of cylcobutane pyrimidine dimers introduced by ultraviolet light (254 nm). SV40 chromatin and purified SV40 DNA (radioactively labeled with different isotopes) were mixed and irradiated in vitro. The proteins were extracted and pyrimidine dimers detected as sites sensitive to the UV-endonuclease encoded by bacteriophage T4. When irradiation was carried out in the presence of at least 0.05 M NaCl the same number of dimers were formed in chromatin as in free DNA. Irradiation in the absence of NaCl, however, reduced the relative yield of dimers in chromatin to 89% of that in free DNA. Different methods of chromatin preparation did not influence these results. (author)

Live cell imaging unveils multiple domain requirements for in vivo dimerization of the glucocorticoid receptor.

Directory of Open Access Journals (Sweden)

Diego M Presman

2014-03-01

Full Text Available Glucocorticoids are essential for life, but are also implicated in disease pathogenesis and may produce unwanted effects when given in high doses. Glucocorticoid receptor (GR transcriptional activity and clinical outcome have been linked to its oligomerization state. Although a point mutation within the GR DNA-binding domain (GRdim mutant has been reported as crucial for receptor dimerization and DNA binding, this assumption has recently been challenged. Here we have analyzed the GR oligomerization state in vivo using the number and brightness assay. Our results suggest a complete, reversible, and DNA-independent ligand-induced model for GR dimerization. We demonstrate that the GRdim forms dimers in vivo whereas adding another mutation in the ligand-binding domain (I634A severely compromises homodimer formation. Contrary to dogma, no correlation between the GR monomeric/dimeric state and transcriptional activity was observed. Finally, the state of dimerization affected DNA binding only to a subset of GR binding sites. These results have major implications on future searches for therapeutic glucocorticoids with reduced side effects.

The crystal structure of 6-(4-chlorophenyl-2-(4-methylbenzylimidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde

Directory of Open Access Journals (Sweden)

A. Sowmya

2016-10-01

Full Text Available In the title imidazo[2,1-b][1,3,4]thiadiazole derivative, C19H14ClN3OS, the 4-methylbenzyl and chlorophenyl rings are inclined to the planar imidazo[2,1-b][1,3,4]thiadiazole moiety (r.m.s. deviation = 0.012 Å by 64.5 (1 and 3.7 (1°, respectively. The molecular structure is primarily stabilized by a strong intramolecular C—H...O hydrogen bond, leading to the formation of a pseudo-seven-membered S(7 ring motif, and a short intramolecular C—H...N contact forming an S(5 ring motif. In the crystal, molecules are linked by pairs of C—H...S hydrogen bonds, forming inversion dimers. The dimers are linked by C—H...O and C—H...π interactions, forming chains propagating along [110].

[Preparation and characterization of Forms A and B of benazepril hydrochloride].

Science.gov (United States)

Fang, Hong; Hu, Xiu-rong; Gu, Jian-ming; Chen, Guan-xi; Feng, Jian-yue; Tang, Gu-ping

2012-11-01

To prepare Form A and Form B of benazepril hydrochloride and to compare the differences in spectrums, thermodynamics and crystal structure between two polymorphic forms. Form A and Form B of benazepril hydrochloride were characterized by Fourier transform infrared spectroscopy (IR), thermal gravimetric analysis (TG), differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD) and single crystal x-ray diffraction (SCXRD). Preparation method, crystal structure and polymorphic stability of Form A and Form B of benazepril hydrochloride were obtained. Based on the analysis of crystal structure of both polymorphs, Form A belonged to monoclone space group P2(1) with a=7.8655(4)Å, b= 11.7700(6)Å, c= 13.5560(7)Å, β= 102.9470(10)°, V=1223.07 (11)Å(3) and Z=2, while Form B belonged to orthorhombic space group P212121, with a=7.9353(8)Å, b=11.6654(11)Å, c=26.6453(16)Å, V=2466.5(4)Å(3) and Z=4. From the DSC and XRD results, Form B of benazepril hydrochloride could be transformed into Form A after heating treatment. Form A and Form B of benazepril hydrochloride are both anhydrous and displayed different polymorphs due to different molecular configuration. Furthermore, Form A exhibits more stable than Form B at high temperatures.

Expression, purification, crystallization and preliminary X-ray crystallographic studies of hepatitis B virus core fusion protein corresponding to octahedral particles

International Nuclear Information System (INIS)

Kikuchi, Masaki; Iwabuchi, Shinichiro; Kikkou, Tatsuhiko; Noguchi, Keiichi; Odaka, Masafumi; Yohda, Masafumi; Kawata, Masaaki; Sato, Chikara; Matsumoto, Osamu

2013-01-01

Novel hepatitis B virus-like particles of recombinant dimeric core–GFP fusion protein were expressed, purified and crystallized. The crystals diffracted to 2.15 Å resolution and belonged to space group F432, with unit-cell parameters a = b = c = 219.7 Å. Recombinant hepatitis B virus core proteins dimerize to form building blocks that are capable of self-assembly into a capsid. A core capsid protein dimer (CPD) linked to a green fluorescent protein variant, EGFP, at the C-terminus has been designed. The recombinant fusion CPD was expressed in Escherichia coli, assembled into virus-like particles (VLPs), purified and crystallized. The single crystal diffracted to 2.15 Å resolution and belonged to the cubic space group F432, with unit-cell parameters a = b = c = 219.7 Å. The fusion proteins assembled into icosahedral VLPs in aqueous solution, but were rearranged into octahedral symmetry through the crystal-packing process under the crystallization conditions

Selective amine catalysed steroidal dimerization

Indian Academy of Sciences (India)

of cholesterol is the formation of a green colour in concentrated sulphuric acid, and this was shown to be due to a polyenyl steroidal dimer carbocation.7–9 Many dimeric and oligomeric steroids exhibit interesting micellular, detergent and liquid crystal behaviour.10,11. Most of the steroidal dimmers are also well-known.

Baculoviral expression and characterization of human recombinant PGCP in the form of an active mature dimer and an inactive precursor protein.

Science.gov (United States)

Zajc, Tajana; Suban, Dejan; Rajković, Jelena; Dolenc, Iztok

2011-02-01

The human-blood plasma glutamate carboxypeptidase (PGCP) is a proteinase that acts on the unsubstituted N- and C-termini of dipeptides. It has been suggested that this PGCP is involved in the release of thyroxine. Furthermore, research has suggested that its activity is up-regulated in hepatitis-C-virus-infected patients with hepatocellular carcinoma. In this study expressed human PGCP in the baculovirus expression system was produced by a Sf9 insect cell line with aim to prepare sufficient amounts of active recombinant enzyme for a subsequent biological characterization. Recombinant PGCP was expressed and secreted into the medium in the form of an inactive proenzyme. It was gradually converted into an active form in the medium after three days, with the highest expression of the active form on day six. The protein was sequentially purified by a combination of various liquid chromatographies, such as hydroxyapatite, ion exchange, and gel chromatography, and as final step with affinity chromatography on Phe-Leu-Sepharose. The human PGCP was purified as an active enzyme in the dimer form and as inactive precursor protein. The dipeptidase activity was confirmed by measuring the hydrolysis of the Ser-Met dipeptide at a slightly acidic pH. Copyright © 2010 Elsevier Inc. All rights reserved.

Photoionization of helium dimers

International Nuclear Information System (INIS)

Havermeier, Tilo

2010-01-01

The helium dimer is one of the most weakly bound systems in the universe. This makes it an interesting quantum mechanical object for investigation. These Van der Waals Clusters can be produced in an expansion of a cryogenic gas jet through a small nozzle into vacuum. In the present experiment we examine the interaction of He dimers with synchrotron radiation at an energy range from 64 to 78 eV. We observed different pathways leading to single ionization of both He atoms of the dimer compound. This two close standing ions begin now to dissociate in cause of their coulomb potential. All charged fragments were detected in coincidence with a COLTRIMS system. Especially Interatomic Coulombic Decay (ICD) and the two step process (TS1) were clearly identified. Furthermore a distribution of the internuclear distance was obtained from the measured Kinetic Energy Release (KER). (orig.)

Pyrimidine dimer formation and repair in human skin

International Nuclear Information System (INIS)

Sutherland, B.M.; Harber, L.C.; Kochevar, I.E.

1980-01-01

Cyclobutyl pyrimidine dimers have been detected in the DNA of human skin following in vivo irradiation with suberythermal doses of ultraviolet (UV) radiation from FS-20 sun lamp fluorescent tubes. Dimers were assayed by treatment of extracted DNA with Micrococus luteus UV-specific endonuclease, alkaline agarose electrophoresis, and ethidum bromide staining. This technique, in contrast to conventional dimer assays, can be used with nonradioactive DNA and is optimal at low UV light doses. These data suggest that some dimer disappearance by excision repair occurs within 20 min of UV irradiation and that photoreactivation of dimers can make a contribution to the total repair process

Adventures in holographic dimer models

International Nuclear Information System (INIS)

Kachru, Shamit; Karch, Andreas; Yaida, Sho

2011-01-01

We abstract the essential features of holographic dimer models, and develop several new applications of these models. Firstly, semi-holographically coupling free band fermions to holographic dimers, we uncover novel phase transitions between conventional Fermi liquids and non-Fermi liquids, accompanied by a change in the structure of the Fermi surface. Secondly, we make dimer vibrations propagate through the whole crystal by way of double trace deformations, obtaining nontrivial band structure. In a simple toy model, the topology of the band structure experiences an interesting reorganization as we vary the strength of the double trace deformations. Finally, we develop tools that would allow one to build, in a bottom-up fashion, a holographic avatar of the Hubbard model.

Thermal and non-thermal lattice gas models for a dimer-trimer surface catalytic reaction: a Monte-Carlo simulation study

International Nuclear Information System (INIS)

Iqbal, K.; Khand, P.A.

2012-01-01

The kinetics of an irreversible dimer-trimer reaction of the type 2 A/sub 3/ +3 B/sub 2/ -- 6 AB by considering the precursor motion of the dimer (B/sub 2) on a square, as well as on a hexagonal surface, by using a Monte Carlo simulation have been studied. When the movement of precursors is limited to the first nearest neighborhood, the model gives reactive window widths of the order of 0.22 and 0.29 for the square and the hexagonal lattices, respectively, which are quite large compared to those predicted by the LH model. In our model, the reactive window width for a square lattice increases significantly as compared to that for the LH models of the same system on square and hexagonal lattices. The width of the reactive region increases when the precursor motion is extended to the second and the third nearest neighborhood. The continuous transition disappears when the precursor motion is extended to the third nearest neighborhood. The diffusion of B atoms does not change the situation qualitatively for both the precursor and the LH models. However, desorption of the dimer changes the situation significantly; i.e., the width of the reactive window shows an exponential growth with respect to the desorption probability of the dimer for both the precursor and the LH models. In our opinion, the inclusion of precursors in the LH model of the dimer-trimer reactions leads to a better and more realistic description of the heterogeneous catalytic reactions. Consequently, further numerical and theoretical activity in this field will be very useful for understanding complex heterogeneous reactions. (orig./A.B.)

Characterization of the UV-crosslinked heterodimer of histones H2B and H4

International Nuclear Information System (INIS)

Johnson, E.R.; Brown, D.M.; DeLange, R.J.

1986-01-01

At relatively high salt concentrations (1.2 M), histone 2B (H2B) and histone 4 (H4) can be covalently crosslinked by irradiation with ultraviolet light to yield a mixture of the three possible dimers: H2B-H2B, H4-H4, and H2B-H4. The formation of the H2B-H4 heterodimer was found to be favored at lower histone concentrations (> 90% H2B-H4 at 0.1 mg/ml total histone protein). CNBr cleavage of the H2B-H4 dimer produced three fragments which were separated by reverse phase HPLC. These fragments were identified by amino acid compositional analysis to be H4(85-102), H2B(62-125), and the crosslinked N-terminal regions H2B(1-59)-H4(1-84). Amino acid sequence analysis of the crosslinked fragment indicated that tyrosine-40 of H2B is likely involved in the covalent crosslinkage which joins the histone monomers to form the heterodimer

Dynamic interplay between adhesive and lateral E-cadherin dimers

DEFF Research Database (Denmark)

Klingelhöfer, Jörg; Laur, Oscar Y; Troyanovsky, Regina B

2002-01-01

M. The disappearance of adhesive dimers was counterbalanced by an increase in Trp156-dependent lateral dimers. Increasing the calcium concentration to a normal level rapidly restored the original balance between adhesive and lateral dimers. We also present evidence that E-cadherin dimers in vivo have a short lifetime...

Direct Assessment of the Effect of the Gly380Arg Achondroplasia Mutation on FGFR3 Dimerization Using Quantitative Imaging FRET

Science.gov (United States)

Placone, Jesse; Hristova, Kalina

2012-01-01

The Gly380Arg mutation in FGFR3 is the genetic cause for achondroplasia (ACH), the most common form of human dwarfism. The mutation has been proposed to increase FGFR3 dimerization, but the dimerization propensities of wild-type and mutant FGFR3 have not been compared. Here we use quantitative imaging FRET to characterize the dimerization of wild-type FGFR3 and the ACH mutant in plasma membrane-derived vesicles from HEK293T cells. We demonstrate a small, but statistically significant increase in FGFR3 dimerization due to the ACH mutation. The data are consistent with the idea that the ACH mutation causes a structural change which affects both the stability and the activity of FGFR3 dimers in the absence of ligand. PMID:23056398

Plasmonic nanospherical dimers for color pixels

KAUST Repository

Alrasheed, Salma

2018-04-20

Display technologies are evolving more toward higher resolution and miniaturization. Plasmonic color pixels can offer solutions to realize such technologies due to their sharp resonances and selective scattering and absorption at particular wavelengths. Metal nanosphere dimers are capable of supporting plasmon resonances that can be tuned to span the entire visible spectrum. In this article, we demonstrate numerically bright color pixels that are highly polarized and broadly tuned using periodic arrays of metal nanosphere dimers on a glass substrate. We show that it is possible to obtain RGB pixels in the reflection mode. The longitudinal plasmon resonance of nanosphere dimers along the axis of the dimer is the main contributor to the color of the pixel, while far-field diffractive coupling further enhances and tunes the plasmon resonance. The computational method used is the finite-difference time-domain method. The advantages of this approach include simplicity of the design, bright coloration, and highly polarized function. In addition, we show that it is possible to obtain different colors by varying the angle of incidence, the periodicity, the size of the dimer, the gap, and the substrate thickness.

Electrophoretic and zymographic techniques for production monitoring of two lipase forms from Candida antarctica DSM 70725

Directory of Open Access Journals (Sweden)

Dimitrijević Aleksandra S.

2012-01-01

Full Text Available Yeast Candida antarctica produces two lipase forms, which are widely used as catalysts in variety of organic reactions, many of which are applied on a large scale. In this work, production of two forms of lipase from C. antarctica DSM 70725 (CAL A and CAL B was monitored during seven days of cultivation in the optimal medium using different electrophoretic and zymographic techniques. According to electrophoresis after silver staining, C. antarctica lipase A (molecular mass 45 kDa was produced starting from the second day of cultivation. C. antarctica lipase B (CAL B was also produced starting from the second day, but protein was present in the fermentation broth predominantly as dimer (molecular weight 66 kDa, while presence of monomeric form of CAL B (molecular weight of 33 kDa was observed starting from the fourth day of cultivation. Both types of zymograms (based on hydrolysis and synthesis reactions were used for detection of lipase activity in the fermentation broth. C. antarctica lipase A showed activity only in hydrolytic zymogram, when α-naphtyl butyrate was used as substrate. In the same zymogram, with α-naphtyl acetate as substrate no CAL A activity was detected. Similarly, CAL A showed no activity in synthesis based zymograms towards oleic acid and octanol as substrates, indicating that CAL A is not active towards very short or long-chain substrates. As opposite of CAL A, both monomeric and dimeric form of CAL B were detected in the all zymograms, suggesting that CAL B is active towards wide range of substrates, regardless to the chain length. Thus, zymogram based on hydrolysis of α-naphtyl butyrate represents a simple method for monitoring the production of two forms of lipase from C. antarctica, that greatly differ in their characteristics.

Antiviral activity of α-helical stapled peptides designed from the HIV-1 capsid dimerization domain

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Cowburn David

2011-05-01

Full Text Available Abstract Background The C-terminal domain (CTD of HIV-1 capsid (CA, like full-length CA, forms dimers in solution and CTD dimerization is a major driving force in Gag assembly and maturation. Mutations of the residues at the CTD dimer interface impair virus assembly and render the virus non-infectious. Therefore, the CTD represents a potential target for designing anti-HIV-1 drugs. Results Due to the pivotal role of the dimer interface, we reasoned that peptides from the α-helical region of the dimer interface might be effective as decoys to prevent CTD dimer formation. However, these small peptides do not have any structure in solution and they do not penetrate cells. Therefore, we used the hydrocarbon stapling technique to stabilize the α-helical structure and confirmed by confocal microscopy that this modification also made these peptides cell-penetrating. We also confirmed by using isothermal titration calorimetry (ITC, sedimentation equilibrium and NMR that these peptides indeed disrupt dimer formation. In in vitro assembly assays, the peptides inhibited mature-like virus particle formation and specifically inhibited HIV-1 production in cell-based assays. These peptides also showed potent antiviral activity against a large panel of laboratory-adapted and primary isolates, including viral strains resistant to inhibitors of reverse transcriptase and protease. Conclusions These preliminary data serve as the foundation for designing small, stable, α-helical peptides and small-molecule inhibitors targeted against the CTD dimer interface. The observation that relatively weak CA binders, such as NYAD-201 and NYAD-202, showed specificity and are able to disrupt the CTD dimer is encouraging for further exploration of a much broader class of antiviral compounds targeting CA. We cannot exclude the possibility that the CA-based peptides described here could elicit additional effects on virus replication not directly linked to their ability to bind

Molecular modelling investigations on the possibility of phenanthrene dimers to be the primary nuclei of soot

Science.gov (United States)

Wei, Mingrui; Wu, Sheng; Li, Fan; Zhang, Dongju; Zhang, Tingting; Guo, Guanlun

2017-11-01

Pyrene dimerisation was successfully used to model the beginning of soot nucleation in some simulation models. However, the quantum mechanics (QM) calculations proved that the binding energy of a PAH dimer with three six-member rings was similar to that of a pyrene dimer. Meanwhile, the high concentration of phenanthrene at flame conditions indicated high probability of collisions among them. The small difference of the binding energy and high concentration indicated that PAHs structurally smaller than pyrene also could be involved in soot inception. Hence, binary collisions of phenanthrene were simulated to find out whether phenanthrene dimers can serve as soot primary nuclei or not by using non-equilibrium molecular dynamics (MD). Three temperatures, six collision orientations and 155 initial translational velocities (ITVs) were considered. The results indicated that the number of dimers with lifetime over 10 ps which can serve as soot nuclei decreased from 52 at 1000 K to 17 at 1600 K, and further to 6 at 2400 K, which means that low temperature was more favourable for phenanthrene to form soot nuclei. Meanwhile, no soot nuclei were formed at the high velocity region (HVR), compared to 43 and 9 at low and middle velocity regions (LVR and MVR), respectively, when temperature was 1000 K. Also, no soot nuclei were formed at HVR when the temperature was raised to 1600 K and 2400 K. This indicated that HVR was unfavourable for phenanthrene to form soot nuclei. The results computationally further illustrated that small PAHs such as phenanthrene could serve as soot primary nuclei, since they have similar mole fractions in some flames. This may be useful for future soot simulation models.

The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion.

Science.gov (United States)

Schulte, Kathrin; Pawlowski, Nikolaus; Faelber, Katja; Fröhlich, Chris; Howard, Jonathan; Daumke, Oliver

2016-03-02

The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis, it has been proposed that the GTPase domains of Irga6 dimerize in an antiparallel fashion during oligomerization. We determined the crystal structure of an oligomerization-impaired Irga6 mutant bound to a non-hydrolyzable GTP analog. Contrary to the previous model, the structure shows that the GTPase domains dimerize in a parallel fashion. The nucleotides in the center of the interface participate in dimerization by forming symmetric contacts with each other and with the switch I region of the opposing Irga6 molecule. The latter contact appears to activate GTP hydrolysis by stabilizing the position of the catalytic glutamate 106 in switch I close to the active site. Further dimerization contacts involve switch II, the G4 helix and the trans stabilizing loop. The Irga6 structure features a parallel GTPase domain dimer, which appears to be a unifying feature of all dynamin and septin superfamily members. This study contributes important insights into the assembly and catalytic mechanisms of IRG proteins as prerequisite to understand their anti-microbial action.

In vitro production of thymine dimer by ultroviolet irradiation of DNA from mesophilic and thermophilic bacteria

International Nuclear Information System (INIS)

Yein, F.S.; Stenesh, J.

1989-01-01

Thymine dimer was produced in vitro by ultraviolet irradiation of DNA, isolated from the mesophile Bacillus licheniformis and the thermophile B. stearothermophilus. Irradiation was performed at three different temperaturs (35, 45 and 55 C) and the thymine dimer was isolated and determined. An HPLC procedure was developed that permitted temperature was greater for the thermophile than for the mesophile. Formation of thymine dimer increased with temperature for both organisms but more so for the thermophile; over the temperature range of 35-55 C, the average increase in thymine dimer production for the themrophile was about 4-times that for the mesophile. The melting out temperature, as a function of increasing irradiation temperature, was essentially unchanged for the mesophilic DNA, but decreased progressively for the thermophilic DNA. These results are discussed in terms of the macromolecular theory of to the macromolecular theory of the thermophily. (author). 31 refs.; 4 figs.; 3 tabs

Van der Waals bond in dimers: H2Ne, H2Ar, H2Kr

International Nuclear Information System (INIS)

Waaijer, M.

1981-01-01

The H 2 -inert gas dimers H 2 X, and particularly H 2 Ne, H 2 Ar and H 2 Kr, form the subject of this thesis and are loosely bound van der Waals complexes, which is reflected in the low number of bound states and the small anisotropic interaction. The H 2 X dimers studied are formed in a supersonic nozzle expansion, in which the internal energy is converted into the macroscopic flow energy, establishing an internal temperature drop to 3 K, which favours dimer formation. Because of this cooling the H 2 X dimers relax to the lowest rotational states. The hyperfine transitions have been measured using magnetic beam resonance and yield information about the isotropic as well as the anisotropic intermolecular potential in the range between the classical turning points and in the adjacent part of the repulsive branch. The sensitivity of the method is very high and slight changes in the intermolecular potential cause significant effects. The analysis of the measured hyperfine transitions incorporates all interacting states of the molecule, bound as well as unbound (continuum) states. For H 2 Ne, which is the best studied H 2 -inert gas system from the experimental point of view, the author succeeded in establishing an intermolecular potential, that provides a solid ground for comparison with future ab initio calculations. (Auth.)

Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Does a Normal Age-Adjusted D-Dimer Rule Out PE?

Directory of Open Access Journals (Sweden)

Jacob Ortiz

2017-01-01

Full Text Available Risk assessment for pulmonary embolism (PE currently relies on physician judgment, clinical decision rules (CDR, and D-dimer testing. There is still controversy regarding the role of D-dimer testing in low or intermediate risk patients. The objective of the study was to define the role of clinical decision rules and D-dimer testing in patients suspected of having a PE. Records of 894 patients referred for computed tomography pulmonary angiography (CTPA at a University medical center were analyzed. The clinical decision rules overall had an ROC of approximately 0.70, while signs of DVT had the highest ROC (0.80. A low probability CDR coupled with a negative age-adjusted D-dimer largely excluded PE. The negative predictive value (NPV of an intermediate CDR was 86–89%, while the addition of a negative D-dimer resulted in NPVs of 94%. Thus, in patients suspected of having a PE, a low or intermediate CDR does not exclude PE; however, in patients with an intermediate CDR, a normal age-adjusted D-dimer increases the NPV.

Crystal structure of a human single domain antibody dimer formed through V(H-V(H non-covalent interactions.

Directory of Open Access Journals (Sweden)

Toya Nath Baral

Full Text Available Single-domain antibodies (sdAbs derived from human V(H are considered to be less soluble and prone to aggregate which makes it difficult to determine the crystal structures. In this study, we isolated and characterized two anti-human epidermal growth factor receptor-2 (HER2 sdAbs, Gr3 and Gr6, from a synthetic human V(H phage display library. Size exclusion chromatography and surface plasmon resonance analyses demonstrated that Gr3 is a monomer, but that Gr6 is a strict dimer. To understand this different molecular behavior, we solved the crystal structure of Gr6 to 1.6 Å resolution. The crystal structure revealed that the homodimer assembly of Gr6 closely mimics the V(H-V(L heterodimer of immunoglobulin variable domains and the dimerization interface is dominated by hydrophobic interactions.

Direct assessment of the effect of the Gly380Arg achondroplasia mutation on FGFR3 dimerization using quantitative imaging FRET.

Directory of Open Access Journals (Sweden)

Jesse Placone

Full Text Available The Gly380Arg mutation in FGFR3 is the genetic cause for achondroplasia (ACH, the most common form of human dwarfism. The mutation has been proposed to increase FGFR3 dimerization, but the dimerization propensities of wild-type and mutant FGFR3 have not been compared. Here we use quantitative imaging FRET to characterize the dimerization of wild-type FGFR3 and the ACH mutant in plasma membrane-derived vesicles from HEK293T cells. We demonstrate a small, but statistically significant increase in FGFR3 dimerization due to the ACH mutation. The data are consistent with the idea that the ACH mutation causes a structural change which affects both the stability and the activity of FGFR3 dimers in the absence of ligand.

Effects of gamma radiation and menadione (vit. K3) on dissolution and dimerization of δ-tocopherol

International Nuclear Information System (INIS)

Kupczyk, B.; Gogolewski, M.

1997-01-01

Effect of ionizing radiation and menadione (vit. K 3 ) on dissolution and dimerization of δ-tocopherol was studied. Mixture of δ-tocopherol and menadione (vit. K 3 ) dissolved in benzene, ethanol or used in substantia were irradiated at 2.5, 5, 10, 20 kGy dose using Co-60 as a radiation source. Dissolution of δ-tocopherol in substantia was lower then disintegration of δ-tocopherol dissolved in benzene or in ethanol. However, we did not observe any significant difference between dissolution of δ-tocopherol in both studied solvents. The number of formed dimers of δ-tocopherol were different for all three cases tested. The quantities of δ-tocopherol dimers were dependent on radiation dose. (author)

Viscosity and sedimentation behaviors of the magnetorheological suspensions with oleic acid/dimer acid as surfactants

Energy Technology Data Exchange (ETDEWEB)

Yang, Jianjian; Yan, Hua; Hu, Zhide; Ding, Ding

2016-11-01

This work deals with the role of polar interactions on the viscosity and sedimentation behaviors of magnetorheological suspensions with micro-sized magnetic particles dispersed in oil carriers. The oleic acid and dimer acid were employed to make an adjustment of the hydrophobicity of iron particles, in the interest of performing a comparative evaluation of the contributions of the surface polarity. The viscosity tests show that the adsorbed surfactant layer may impose a hindrance to the movement of iron particles in the oil medium. The polar attractions between dimer acid covered particles gave rise to a considerable increase in viscosity, indicating flocculation structure developed in the suspensions. The observed plateau-like region in the vicinity of 0.1 s{sup −1} for MRF containing dimer acid is possibly due to the flocculation provoked by the carboxylic polar attraction, in which the structure is stable against fragmentation. Moreover, a quick recovery of the viscosity and a higher viscosity-temperature index also suggest the existence of particle-particle polar interaction in the suspensions containing dimer acid. The sedimentation measurements reveal that the steric repulsion of oleic acid plays a limited role in the stability of suspensions only if a large quantity of surfactant was used. The sedimentation results observed in the dimer acid covered particles confirm that loose and open flocculation was formed and enhanced sedimentation stability. - Highlights: • Surfactants were employed to make adjustments of the hydrophobicity of particles. • Polar attractions between particles increased the viscosity considerably. • Loose and open flocculation was formed in CI/DA suspension. • The steric repulsion of oleic acid played a limited role in the stability.

6-Bromo-1,3-di-2-propynyl-1H-imidazo[4,5-b]pyridin-2(3H-one

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S. Dahmani

2010-04-01

Full Text Available The room-temperature reaction of propargyl bromide and 6-bromo-1,3-dihydroimidazo[4,5-b]pyridin-2-one in dimethylformamide yields the title compound, C12H8BrN3O, which features nitrogen-bound propynyl substituents. The imidazopyridine fused ring is almost planar (r.m.s. deviation = 0.011 Å; the propynyl chains point in opposite directions relative to the fused ring. One acetylenic H atom is hydrogen bonded to the carbonyl O atom of an inversion-related molecule, forming a dimer; adjacent dimers are linked by a second acetylene–pyridine C—H...N interaction, forming a layer motif.

Critical structural and functional roles for the N-terminal insertion sequence in surfactant protein B analogs.

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Frans J Walther

2010-01-01

Full Text Available Surfactant protein B (SP-B; 79 residues belongs to the saposin protein superfamily, and plays functional roles in lung surfactant. The disulfide cross-linked, N- and C-terminal domains of SP-B have been theoretically predicted to fold as charged, amphipathic helices, suggesting their participation in surfactant activities. Earlier structural studies with Mini-B, a disulfide-linked construct based on the N- and C-terminal regions of SP-B (i.e., approximately residues 8-25 and 63-78, confirmed that these neighboring domains are helical; moreover, Mini-B retains critical in vitro and in vivo surfactant functions of the native protein. Here, we perform similar analyses on a Super Mini-B construct that has native SP-B residues (1-7 attached to the N-terminus of Mini-B, to test whether the N-terminal sequence is also involved in surfactant activity.FTIR spectra of Mini-B and Super Mini-B in either lipids or lipid-mimics indicated that these peptides share similar conformations, with primary alpha-helix and secondary beta-sheet and loop-turns. Gel electrophoresis demonstrated that Super Mini-B was dimeric in SDS detergent-polyacrylamide, while Mini-B was monomeric. Surface plasmon resonance (SPR, predictive aggregation algorithms, and molecular dynamics (MD and docking simulations further suggested a preliminary model for dimeric Super Mini-B, in which monomers self-associate to form a dimer peptide with a "saposin-like" fold. Similar to native SP-B, both Mini-B and Super Mini-B exhibit in vitro activity with spread films showing near-zero minimum surface tension during cycling using captive bubble surfactometry. In vivo, Super Mini-B demonstrates oxygenation and dynamic compliance that are greater than Mini-B and compare favorably to full-length SP-B.Super Mini-B shows enhanced surfactant activity, probably due to the self-assembly of monomer peptide into dimer Super Mini-B that mimics the functions and putative structure of native SP-B.

Even-odd alternation of the formation of dimer isomers in irradiated polycrystalline alkanes: evidence from product analysis

International Nuclear Information System (INIS)

Baudson, T.; Tilquin, B.

1984-01-01

Recent ESR studies on n-alkanes from n-C 11 to n-C 25 have shown that a prominent chain end (-CH 2 -CH 2 ) alkyl radical is formed in odd members of the series. In this preliminary discussion of our study, we shall report the capillary chromatogram in the dimer isomers range for n-alkanes ranging from n-C 11 to n-C 17 irradiated at 80 kGy. Dimer isomers, produced in part by the combination of chain end radicals, are eluted at the end chromatogram. The combination of two chain end radicals gives the dimer (D 11 ) isomer eluted at the last place. It is shown that dimers produced by the combination of chain end alkyl radicals are more important for the odd members of the series than for the even members. (author)

Atomic resolution crystal structure of VcLMWPTP-1 from Vibrio cholerae O395: Insights into a novel mode of dimerization in the low molecular weight protein tyrosine phosphatase family

Energy Technology Data Exchange (ETDEWEB)

Nath, Seema; Banerjee, Ramanuj; Sen, Udayaditya, E-mail: udayaditya.sen@saha.ac.in

2014-07-18

Highlights: • VcLMWPTP-1 forms dimer in solution. • The dimer is catalytically active unlike other reported dimeric LMWPTPs. • The formation of extended dimeric surface excludes the active site pocket. • The surface bears closer resemblance to eukaryotic LMWPTPs. - Abstract: Low molecular weight protein tyrosine phosphatase (LMWPTP) is a group of phosphotyrosine phosphatase ubiquitously found in a wide range of organisms ranging from bacteria to mammals. Dimerization in the LMWPTP family has been reported earlier which follows a common mechanism involving active site residues leading to an enzymatically inactive species. Here we report a novel form of dimerization in a LMWPTP from Vibrio cholera 0395 (VcLMWPTP-1). Studies in solution reveal the existence of the dimer in solution while kinetic study depicts the active form of the enzyme. This indicates that the mode of dimerization in VcLMWPTP-1 is different from others where active site residues are not involved in the process. A high resolution (1.45 Å) crystal structure of VcLMWPTP-1 confirms a different mode of dimerization where the active site is catalytically accessible as evident by a tightly bound substrate mimicking ligand, MOPS at the active site pocket. Although being a member of a prokaryotic protein family, VcLMWPTP-1 structure resembles very closely to LMWPTP from a eukaryote, Entamoeba histolytica. It also delineates the diverse surface properties around the active site of the enzyme.

Conformational study of the protegrin-1 (PG-1 dimer interaction with lipid bilayers and its effect

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Nussinov Ruth

2007-04-01

Full Text Available Abstract Background Protegrin-1 (PG-1 is known as a potent antibiotic peptide; it prevents infection via an attack on the membrane surface of invading microorganisms. In the membrane, the peptide forms a pore/channel through oligomerization of multiple subunits. Recent experimental and computational studies have increasingly unraveled the molecular-level mechanisms underlying the interactions of the PG-1 β-sheet motifs with the membrane. The PG-1 dimer is important for the formation of oligomers, ordered aggregates, and for membrane damaging effects. Yet, experimentally, different dimeric behavior has been observed depending on the environment: antiparallel in the micelle environment, and parallel in the POPC bilayer. The experimental structure of the PG-1 dimer is currently unavailable. Results Although the β-sheet structures of the PG-1 dimer are less stable in the bulk water environment, the dimer interface is retained by two intermolecular hydrogen bonds. The formation of the dimer in the water environment implies that the pathway of the dimer invasion into the membrane can originate from the bulk region. In the initial contact with the membrane, both the antiparallel and parallel β-sheet conformations of the PG-1 dimer are well preserved at the amphipathic interface of the lipid bilayer. These β-sheet structures illustrate the conformations of PG-1 dimer in the early stage of the membrane attack. Here we observed that the activity of PG-1 β-sheets on the bilayer surface is strongly correlated with the dimer conformation. Our long-term goal is to provide a detailed mechanism of the membrane-disrupting effects by PG-1 β-sheets which are able to attack the membrane and eventually assemble into the ordered aggregates. Conclusion In order to understand the dimeric effects leading to membrane damage, extensive molecular dynamics (MD simulations were performed for the β-sheets of the PG-1 dimer in explicit water, salt, and lipid bilayers

32 CFR Appendix B to Part 45 - DD Form 214ws

Science.gov (United States)

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false DD Form 214ws B Appendix B to Part 45 National... CERTIFICATE OF RELEASE OR DISCHARGE FROM ACTIVE DUTY (DD FORM 214/5 SERIES) Pt. 45, App. B Appendix B to Part 45—DD Form 214ws EC23OC91.007 ...

Mahler Measure, Eisenstein Series and Dimers

NARCIS (Netherlands)

Stienstra, J.

2007-01-01

This note reveals a mysterious link between the partition function of certain dimer models on 2-dimensional tori and the L-function of their spectral curves. It also relates the partition function in certain families of dimer models to Eisenstein series. http://www.arxiv.org/abs/math.NT/0502197

RecFOR Is Not Required for Pneumococcal Transformation but Together with XerS for Resolution of Chromosome Dimers Frequently Formed in the Process

Science.gov (United States)

Johnston, Calum; Mortier-Barrière, Isabelle; Granadel, Chantal; Polard, Patrice; Martin, Bernard; Claverys, Jean-Pierre

2015-01-01

Homologous recombination (HR) is required for both genome maintenance and generation of diversity in eukaryotes and prokaryotes. This process initiates from single-stranded (ss) DNA and is driven by a universal recombinase, which promotes strand exchange between homologous sequences. The bacterial recombinase, RecA, is loaded onto ssDNA by recombinase loaders, RecBCD and RecFOR for genome maintenance. DprA was recently proposed as a third loader dedicated to genetic transformation. Here we assessed the role of RecFOR in transformation of the human pathogen Streptococcus pneumoniae. We firstly established that RecFOR proteins are not required for plasmid transformation, strongly suggesting that DprA ensures annealing of plasmid single-strands internalized in the process. We then observed no reduction in chromosomal transformation using a PCR fragment as donor, contrasting with the 10,000-fold drop in dprA - cells and demonstrating that RecFOR play no role in transformation. However, a ∼1.45-fold drop in transformation was observed with total chromosomal DNA in recFOR mutants. To account for this limited deficit, we hypothesized that transformation with chromosomal DNA stimulated unexpectedly high frequency (>30% of cells) formation of chromosome dimers as an intermediate in the generation of tandem duplications, and that RecFOR were crucial for dimer resolution. We validated this hypothesis, showing that the site-specific recombinase XerS was also crucial for dimer resolution. An even higher frequency of dimer formation (>80% of cells) was promoted by interspecies transformation with Streptococcus mitis chromosomal DNA, which contains numerous inversions compared to pneumococcal chromosome, each potentially promoting dimerization. In the absence of RecFOR and XerS, dimers persist, as confirmed by DAPI staining, and can limit the efficiency of transformation, since resulting in loss of transformant chromosome. These findings strengthen the view that different HR

RecFOR is not required for pneumococcal transformation but together with XerS for resolution of chromosome dimers frequently formed in the process.

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Calum Johnston

2015-01-01

Full Text Available Homologous recombination (HR is required for both genome maintenance and generation of diversity in eukaryotes and prokaryotes. This process initiates from single-stranded (ss DNA and is driven by a universal recombinase, which promotes strand exchange between homologous sequences. The bacterial recombinase, RecA, is loaded onto ssDNA by recombinase loaders, RecBCD and RecFOR for genome maintenance. DprA was recently proposed as a third loader dedicated to genetic transformation. Here we assessed the role of RecFOR in transformation of the human pathogen Streptococcus pneumoniae. We firstly established that RecFOR proteins are not required for plasmid transformation, strongly suggesting that DprA ensures annealing of plasmid single-strands internalized in the process. We then observed no reduction in chromosomal transformation using a PCR fragment as donor, contrasting with the 10,000-fold drop in dprA- cells and demonstrating that RecFOR play no role in transformation. However, a ∼1.45-fold drop in transformation was observed with total chromosomal DNA in recFOR mutants. To account for this limited deficit, we hypothesized that transformation with chromosomal DNA stimulated unexpectedly high frequency (>30% of cells formation of chromosome dimers as an intermediate in the generation of tandem duplications, and that RecFOR were crucial for dimer resolution. We validated this hypothesis, showing that the site-specific recombinase XerS was also crucial for dimer resolution. An even higher frequency of dimer formation (>80% of cells was promoted by interspecies transformation with Streptococcus mitis chromosomal DNA, which contains numerous inversions compared to pneumococcal chromosome, each potentially promoting dimerization. In the absence of RecFOR and XerS, dimers persist, as confirmed by DAPI staining, and can limit the efficiency of transformation, since resulting in loss of transformant chromosome. These findings strengthen the view that

Super-pnicogen bonding in the radical anion of the fluorophosphine dimer

Science.gov (United States)

Setiawan, Dani; Cremer, Dieter

2016-10-01

The LUMO of the pnicogen-bonded fluoro-phosphine dimer has PP bonding character. Radical anion and dianion form relatively strong pnicogen bonds with some covalent character where however the dianion turns out to be a second order transition state. The binding energy of (FPH 2)2- is 30.4 kcal/mol (CCSD(T)/aug-cc-pVTZ; CASPT2(5,8): 30.7 kcal/mol) and the bond strength order measured with the local PP bond stretching force constant increases from 0.055 for the neutral dimer to 0.187 thus revealing that the stabilization of the radical anion is to a large extend a result of one-electron six-center delocalization. Pnicogen-bonded complexes have a stabilizing electron affinity.

Effects of Dimers on Cooperation in the Spatial Prisoner's Dilemma Game

International Nuclear Information System (INIS)

Li Haihong; Cheng Hongyan; Dai Qionglin; Ju Ping; Yang Junzhong; Zhang Mei

2011-01-01

We investigate the evolutionary prisoner's dilemma game in structured populations by introducing dimers, which are defined as that two players in each dimer always hold a same strategy. We find that influences of dimers on cooperation depend on the type of dimers and the population structure. For those dimers in which players interact with each other, the cooperation level increases with the number of dimers though the cooperation improvement level depends on the type of network structures. On the other hand, the dimers, in which there are not mutual interactions, will not do any good to the cooperation level in a single community, but interestingly, will improve the cooperation level in a population with two communities. We explore the relationship between dimers and self-interactions and find that the effects of dimers are similar to that of self-interactions. Also, we find that the dimers, which are established over two communities in a multi-community network, act as one type of interaction through which information between communities is communicated by the requirement that two players in a dimer hold a same strategy. (general)

The properties of B-form monoamine oxidase in mitochondria from monkey platelet.

Science.gov (United States)

Obata, Toshio; Aomine, Masahiro

The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.

Structure of the Mature Streptococcal Cysteine Protease Exotoxin mSpeB in Its Active Dimeric Form

DEFF Research Database (Denmark)

Olsen, Johan G; Dagil, Robert; Niclasen, Louise Meinert

2009-01-01

Invasive infections of Streptococcus pyogenes are dependent on the cysteine protease streptococcal pyrogenic exotoxin B. Previous structures of the enzyme have not disclosed the proper active-site configuration. Here, the crystal structure of the mature enzyme is presented to 1.55 A, disclosing...

Self-association of an indole based guanidinium-carboxylate-zwitterion: formation of stable dimers in solution and the solid state

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Carolin Rether

2010-01-01

Full Text Available The indole based zwitterion 2 forms stable dimers held together by H-bond assisted ion pairs. Dimerisation was confirmed in the solid state and studied in solution using dilution NMR experiments. Even though zwitterion 2 forms very stable dimers even in DMSO, their stability is lower than of an analogous pyrrole based zwitterion 1. As revealed by the X-ray crystal structure the two binding sites in 2 cannot be planar due to steric interactions between the guanidinium group and a neighbouring aromatic CH. Hence the guanidinium moiety is twisted out of planarity from the rest of the molecule forcing the two monomers in dimer 2·2 to interact in a non-ideal orientation. Furthermore, the acidity of the NHs is lower than in 1 (as determined by UV-pH-titration also leading to less efficient binding interactions.

Kinetics of DNA tile dimerization.

Science.gov (United States)

Jiang, Shuoxing; Yan, Hao; Liu, Yan

2014-06-24

Investigating how individual molecular components interact with one another within DNA nanoarchitectures, both in terms of their spatial and temporal interactions, is fundamentally important for a better understanding of their physical behaviors. This will provide researchers with valuable insight for designing more complex higher-order structures that can be assembled more efficiently. In this report, we examined several spatial factors that affect the kinetics of bivalent, double-helical (DH) tile dimerization, including the orientation and number of sticky ends (SEs), the flexibility of the double helical domains, and the size of the tiles. The rate constants we obtained confirm our hypothesis that increased nucleation opportunities and well-aligned SEs accelerate tile-tile dimerization. Increased flexibility in the tiles causes slower dimerization rates, an effect that can be reversed by introducing restrictions to the tile flexibility. The higher dimerization rates of more rigid tiles results from the opposing effects of higher activation energies and higher pre-exponential factors from the Arrhenius equation, where the pre-exponential factor dominates. We believe that the results presented here will assist in improved implementation of DNA tile based algorithmic self-assembly, DNA based molecular robotics, and other specific nucleic acid systems, and will provide guidance to design and assembly processes to improve overall yield and efficiency.

Dimers in Piecewise Temperleyan Domains

Science.gov (United States)

Russkikh, Marianna

2018-03-01

We study the large-scale behavior of the height function in the dimer model on the square lattice. Richard Kenyon has shown that the fluctuations of the height function on Temperleyan discretizations of a planar domain converge in the scaling limit (as the mesh size tends to zero) to the Gaussian Free Field with Dirichlet boundary conditions. We extend Kenyon's result to a more general class of discretizations. Moreover, we introduce a new factorization of the coupling function of the double-dimer model into two discrete holomorphic functions, which are similar to discrete fermions defined in Smirnov (Proceedings of the international congress of mathematicians (ICM), Madrid, Spain, 2006; Ann Math (2) 172:1435-1467, 2010). For Temperleyan discretizations with appropriate boundary modifications, the results of Kenyon imply that the expectation of the double-dimer height function converges to a harmonic function in the scaling limit. We use the above factorization to extend this result to the class of all polygonal discretizations, that are not necessarily Temperleyan. Furthermore, we show that, quite surprisingly, the expectation of the double-dimer height function in the Temperleyan case is exactly discrete harmonic (for an appropriate choice of Laplacian) even before taking the scaling limit.

Diatomic substitutionals in superconducting Nb{sub (1-x)}B{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Farrell, H.H. [Idaho National Laboratory, Materials Science Department, 2525 N. Freemont Ave., MS-2211, P.O. Box 1625, Idaho Falls, ID 83415-2211 (United States)]. E-mail: Helen.Farrell@inl.gov; LaViolette, Randall A. [Idaho National Laboratory, Materials Science Department, 2525 N. Freemont Ave., MS-2211, P.O. Box 1625, Idaho Falls, ID 83415-2211 (United States); Lillo, T.M. [Idaho National Laboratory, Materials Science Department, 2525 N. Freemont Ave., MS-2211, P.O. Box 1625, Idaho Falls, ID 83415-2211 (United States)

2006-11-01

Using first-principles, density functional theory calculations, we have shown that the increase in superconducting critical temperature to above 9 K experimentally observed for B-rich, off-stoichiometry NbB{sub 2} material is associated with the formation of B-dimers on Nb sites rather than with the formation of Nb vacancies, as previously proposed. Our calculations show that certain of these B-dimer configurations have lower binding energies than do the vacancy structures. This result is pressure independent in the range between 0 and 10 GPa, and above. Further, the dimer-containing materials have a higher electronic density of states at the Fermi level than do the vacancy structures. Finally, the presence of B-dimers results in the splitting off of phonon normal modes. These last two factors are relevant to the improved superconducting properties.

Control activity of yeast geranylgeranyl diphosphate synthase from dimer interface through H-bonds and hydrophobic interaction.

Science.gov (United States)

Chang, Chih-Kang; Teng, Kuo-Hsun; Lin, Sheng-Wei; Chang, Tao-Hsin; Liang, Po-Huang

2013-04-23

Previously we showed that yeast geranylgeranyl diphosphate synthase (GGPPS) becomes an inactive monomer when the first N-terminal helix involved in dimerization is deleted. This raises questions regarding why dimerization is required for GGPPS activity and which amino acids in the dimer interface are essential for dimerization-mediated activity. According to the GGPPS crystal structure, three amino acids (N101, N104, and Y105) located in the helix F of one subunit are near the active site of the other subunit. As presented here, when these residues were replaced individually with Ala caused insignificant activity changes, N101A/Y105A and N101A/N104A but not N104A/Y105A showed remarkably decreased k(cat) values (200-250-fold). The triple mutant N101A/N104A/Y105A displayed no detectable activity, although dimer was retained in these mutants. Because N101 and Y105 form H-bonds with H139 and R140 in the other subunit, respectively, we generated H139A/R140A double mutant and found it was inactive and became monomeric. Therefore, the multiple mutations apparently influence the integrity of the catalytic site due to the missing H-bonding network. Moreover, Met111, also on the highly conserved helix F, was necessary for dimer formation and enzyme activity. When Met111 was replaced with Glu, the negative-charged repulsion converted half of the dimer into a monomer. In conclusion, the H-bonds mainly through N101 for maintaining substrate binding stability and the hydrophobic interaction of M111 in dimer interface are essential for activity of yeast GGPPS.

Dimer-based model for heptaspanning membrane receptors.

Science.gov (United States)

Franco, Rafael; Casadó, Vicent; Mallol, Josefa; Ferré, Sergi; Fuxe, Kjell; Cortés, Antonio; Ciruela, Francisco; Lluis, Carmen; Canela, Enric I

2005-07-01

The existence of intramembrane receptor-receptor interactions for heptaspanning membrane receptors is now fully accepted, but a model considering dimers as the basic unit that binds to two ligand molecules is lacking. Here, we propose a two-state-dimer model in which the ligand-induced conformational changes from one component of the dimer are communicated to the other. Our model predicts cooperativity in binding, which is relevant because the other current models fail to address this phenomenon satisfactorily. Our two-state-dimer model also predicts the variety of responses elicited by full or partial agonists, neutral antagonists and inverse agonists. This model can aid our understanding of the operation of heptaspanning receptors and receptor channels, and, potentially, be important for improving the treatment of cardiovascular, neurological and neuropsychyatric diseases.

Cis elements and trans-acting factors involved in the RNA dimerization of the human immunodeficiency virus HIV-1.

Science.gov (United States)

Darlix, J L; Gabus, C; Nugeyre, M T; Clavel, F; Barré-Sinoussi, F

1990-12-05

The retroviral genome consists of two identical RNA molecules joined at their 5' ends by the Dimer Linkage Structure (DLS). To study the mechanism of dimerization and the DLS of HIV-1 RNA, large amounts of bona fide HIV-1 RNA and of mutants have been synthesized in vitro. We report that HIV-1 RNA forms dimeric molecules and that viral nucleocapsid (NC) protein NCp15 greatly activates dimerization. Deletion mutagenesis in the RNA 5' 1333 nucleotides indicated that a small domain of 100 nucleotides, located between positions 311 to 415 from the 5' end, is necessary and sufficient to promote HIV-1 RNA dimerization. This dimerization domain encompasses an encapsidation element located between the 5' splice donor site and initiator AUG of gag and shows little sequence variations in different strains of HIV-1. Furthermore, cross-linking analysis of the interactions between NC and HIV-1 RNA (311 to 415) locates a major contact site in the encapsidation element of HIV-1 RNA. The genomic RNA dimer is tightly associated with nucleocapsid protein molecules in avian and murine retroviruses, and this ribonucleoprotein structure is believed to be the template for reverse transcription. Genomic RNA-protein interactions have been analyzed in human immunodeficiency virus (HIV) virions and results showed that NC protein molecules are tightly bound to the genomic RNA dimer. Since retroviral RNA dimerization and packaging appear to be under the control of the same cis element, the encapsidation sequences, and trans-acting factor, the NC protein, they are probably related events in the course of virion assembly.

Dimerization interface of 3-hydroxyacyl-CoA dehydrogenase tunes the formation of its catalytic intermediate.

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Yingzhi Xu

Full Text Available 3-Hydroxyacyl-CoA dehydrogenase (HAD, EC 1.1.1.35 is a homodimeric enzyme localized in the mitochondrial matrix, which catalyzes the third step in fatty acid β-oxidation. The crystal structures of human HAD and subsequent complexes with cofactor/substrate enabled better understanding of HAD catalytic mechanism. However, numerous human diseases were found related to mutations at HAD dimerization interface that is away from the catalytic pocket. The role of HAD dimerization in its catalytic activity needs to be elucidated. Here, we solved the crystal structure of Caenorhabditis elegans HAD (cHAD that is highly conserved to human HAD. Even though the cHAD mutants (R204A, Y209A and R204A/Y209A with attenuated interactions on the dimerization interface still maintain a dimerization form, their enzymatic activities significantly decrease compared to that of the wild type. Such reduced activities are in consistency with the reduced ratios of the catalytic intermediate formation. Further molecular dynamics simulations results reveal that the alteration of the dimerization interface will increase the fluctuation of a distal region (a.a. 60-80 that plays an important role in the substrate binding. The increased fluctuation decreases the stability of the catalytic intermediate formation, and therefore the enzymatic activity is attenuated. Our study reveals the molecular mechanism about the essential role of the HAD dimerization interface in its catalytic activity via allosteric effects.

A High-Resolution Crystal Structure of a Psychrohalophilic α-Carbonic Anhydrase from Photobacterium profundum Reveals a Unique Dimer Interface.

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Vijayakumar Somalinga

Full Text Available Bacterial α-carbonic anhydrases (α-CA are zinc containing metalloenzymes that catalyze the rapid interconversion of CO2 to bicarbonate and a proton. We report the first crystal structure of a pyschrohalophilic α-CA from a deep-sea bacterium, Photobacterium profundum. Size exclusion chromatography of the purified P. profundum α-CA (PprCA reveals that the protein is a heterogeneous mix of monomers and dimers. Furthermore, an "in-gel" carbonic anhydrase activity assay, also known as protonography, revealed two distinct bands corresponding to monomeric and dimeric forms of PprCA that are catalytically active. The crystal structure of PprCA was determined in its native form and reveals a highly conserved "knot-topology" that is characteristic of α-CA's. Similar to other bacterial α-CA's, PprCA also crystallized as a dimer. Furthermore, dimer interface analysis revealed the presence of a chloride ion (Cl- in the interface which is unique to PprCA and has not been observed in any other α-CA's characterized so far. Molecular dynamics simulation and chloride ion occupancy analysis shows 100% occupancy for the Cl- ion in the dimer interface. Zinc coordinating triple histidine residues, substrate binding hydrophobic patch residues, and the hydrophilic proton wire residues are highly conserved in PprCA and are identical to other well-studied α-CA's.

Hydrodynamic Torques and Rotations of Superparamagnetic Bead Dimers

Science.gov (United States)

Pease, Christopher; Etheridge, J.; Wijesinghe, H. S.; Pierce, C. J.; Prikockis, M. V.; Sooryakumar, R.

Chains of micro-magnetic particles are often rotated with external magnetic fields for many lab-on-a-chip technologies such as transporting beads or mixing fluids. These applications benefit from faster responses of the actuated particles. In a rotating magnetic field, the magnetization of superparamagnetic beads, created from embedded magnetic nano-particles within a polymer matrix, is largely characterized by induced dipoles mip along the direction of the field. In addition there is often a weak dipole mop that orients out-of-phase with the external rotating field. On a two-bead dimer, the simplest chain of beads, mop contributes a torque Γm in addition to the torque from mip. For dimers with beads unbound to each other, mop rotates individual beads which generate an additional hydrodynamic torque on the dimer. Whereas, mop directly torques bound dimers. Our results show that Γm significantly alters the average frequency-dependent dimer rotation rate for both bound and unbound monomers and, when mop exceeds a critical value, increases the maximum dimer rotation frequency. Models that include magnetic and hydrodynamics torques provide good agreement with the experimental findings over a range of field frequencies.

Nitrobenzene anti-parallel dimer formation in non-polar solvents

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Toshiyuki Shikata

2014-06-01

Full Text Available We investigated the dielectric and depolarized Rayleigh scattering behaviors of nitrobenzene (NO2-Bz, which is a benzene mono-substituted with a planar molecular frame bearing the large electric dipole moment 4.0 D, in non-polar solvents solutions, such as tetrachloromethane and benzene, at up to 3 THz for the dielectric measurements and 8 THz for the scattering experiments at 20 °C. The dielectric relaxation strength of the system was substantially smaller than the proportionality to the concentration in a concentrated regime and showed a Kirkwood correlation factor markedly lower than unity; gK ∼ 0.65. This observation revealed that NO2-Bz has a tendency to form dimers, (NO2-Bz2, in anti-parallel configurations for the dipole moment with increasing concentration of the two solvents. Both the dielectric and scattering data exhibited fast and slow Debye-type relaxation modes with the characteristic time constants ∼7 and ∼50 ps in a concentrated regime (∼15 and ∼30 ps in a dilute regime, respectively. The fast mode was simply attributed to the rotational motion of the (monomeric NO2-Bz. However, the magnitude of the slow mode was proportional to the square of the concentration in the dilute regime; thus, the mode was assigned to the anti-parallel dimer, (NO2-Bz2, dissociation process, and the slow relaxation time was attributed to the anti-parallel dimer lifetime. The concentration dependencies of both the dielectric and scattering data show that the NO2-Bz molecular processes are controlled through a chemical equilibrium between monomers and anti-parallel dimers, 2NO2-Bz ↔ (NO2-Bz2, due to a strong dipole-dipole interaction between nitro groups.

Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

Energy Technology Data Exchange (ETDEWEB)

Pham, Anh; Bortolazzo, Anthony [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States); White, J. Brandon, E-mail: Brandon.White@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States)

2012-10-19

Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

International Nuclear Information System (INIS)

Pham, Anh; Bortolazzo, Anthony; White, J. Brandon

2012-01-01

Highlights: ► Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. ► Quercetin forms a heterodimer through oxidation in media with serum. ► The quercetin heterodimer does not kill MDA-MB-231 cells. ► Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. ► Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin’s ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

The dynamics of a polariton dimer in a disordered coupled array of cavities

Science.gov (United States)

Aiyejina, Abuenameh; Andrews, Roger

2018-03-01

We investigate the effect of disorder in the laser intensity on the dynamics of dark-state polaritons in an array of 20 cavities, each containing an ensemble of four-level atoms that is described by a Bose-Hubbard Hamiltonian. We examine the evolution of the polariton number in the cavities starting from a state with either one or two polaritons in one of the cavities. For the case of a single polariton without disorder in the laser intensity, we calculate the wavefunction of the polariton and find that it disperses away from the initial cavity with time. The addition of disorder results in minimal suppression of the dispersal of the wavefunction. In the case of two polaritons with an on-site repulsion to hopping strength ratio of 20, we find that the polaritons form a repulsively bound state or dimer. Without disorder the dimer wavefunction disperses similarly to the single polariton wavefunction but over a longer time period. The addition of sufficiently strong disorder results in localization of the polariton dimer. The localization length is found to be described by a power law with exponent - 1.31. We also find that we can localise the dimer at any given time by switching on the disorder.

The yeast cell fusion protein Prm1p requires covalent dimerization to promote membrane fusion.

Directory of Open Access Journals (Sweden)

Alex Engel

2010-05-01

Full Text Available Prm1p is a multipass membrane protein that promotes plasma membrane fusion during yeast mating. The mechanism by which Prm1p and other putative regulators of developmentally controlled cell-cell fusion events facilitate membrane fusion has remained largely elusive. Here, we report that Prm1p forms covalently linked homodimers. Covalent Prm1p dimer formation occurs via intermolecular disulfide bonds of two cysteines, Cys-120 and Cys-545. PRM1 mutants in which these cysteines have been substituted are fusion defective. These PRM1 mutants are normally expressed, retain homotypic interaction and can traffic to the fusion zone. Because prm1-C120S and prm1-C545S mutants can form covalent dimers when coexpressed with wild-type PRM1, an intermolecular C120-C545 disulfide linkage is inferred. Cys-120 is adjacent to a highly conserved hydrophobic domain. Mutation of a charged residue within this hydrophobic domain abrogates formation of covalent dimers, trafficking to the fusion zone, and fusion-promoting activity. The importance of intermolecular disulfide bonding informs models regarding the mechanism of Prm1-mediated cell-cell fusion.

Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1)*

Science.gov (United States)

Zhuo, You; Yang, Jeong-Yeh; Moremen, Kelley W.; Prestegard, James H.

2016-01-01

Human carcinoembryonic antigen-related cell adhesion molecule 1 (C?/Au: EACAM1) is a cell-surface signaling molecule involved in cell adhesion, proliferation, and immune response. It is also implicated in cancer angiogenesis, progression, and metastasis. This diverse set of effects likely arises as a result of the numerous homophilic and heterophilic interactions that CEACAM1 can have with itself and other molecules. Its N-terminal Ig variable (IgV) domain has been suggested to be a principal player in these interactions. Previous crystal structures of the β-sandwich-like IgV domain have been produced using Escherichia coli-expressed material, which lacks native glycosylation. These have led to distinctly different proposals for dimer interfaces, one involving interactions of ABED β-strands and the other involving GFCC′C″ β-strands, with the former burying one prominent glycosylation site. These structures raise questions as to which form may exist in solution and what the effect of glycosylation may have on this form. Here, we use NMR cross-correlation measurements to examine the effect of glycosylation on CEACAM1-IgV dimerization and use residual dipolar coupling (RDC) measurements to characterize the solution structure of the non-glycosylated form. Our findings demonstrate that even addition of a single N-linked GlcNAc at potential glycosylation sites inhibits dimer formation. Surprisingly, RDC data collected on E. coli expressed material in solution indicate that a dimer using the non-glycosylated GFCC′C″ interface is preferred even in the absence of glycosylation. The results open new questions about what other factors may facilitate dimerization of CEACAM1 in vivo, and what roles glycosylation may play in heterophylic interactions. PMID:27471271

D-dimer Test

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... 1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition]. Pagana, Kathleen D. & Pagana, ... www.itxm.org . Titus, K. (2003 January). Identity crisis persists: which D-dimer? CAP Today , In the ...

Molecular mechanics calculations on cobalt phthalocyanine dimers

NARCIS (Netherlands)

Heuts, J.P.A.; Schipper, E.T.W.M.; Piet, P.; German, A.L.

1995-01-01

In order to obtain insight into the structure of cobalt phthalocyanine dimers, molecular mechanics calculations were performed on dimeric cobalt phthalocyanine species. Molecular mechanics calculations are first presented on monomeric cobalt(II) phthalocyanine. Using the Tripos force field for the

99mTc-labeling of HYNIC-conjugated cyclic RGDfK dimer and tetramer using EDDA as coligand.

Science.gov (United States)

Wang, Jianjun; Kim, Young-Seung; Liu, Shuang

2008-03-01

In this study, EDDA (ethylenediamine- N, N'-diacetic acid) was used as the coligand for 99mTc-labeling of cyclic RGDfK conjugates: HYNIC-dimer (HYNIC = 6-hydrazinonicotinamide; dimer = E[c(RGDfK)]2) and HYNIC-tetramer (tetramer = E{E[c(RGDfK)]2}2). First, HYNIC-dimer was allowed to react with 99mTcO4 (-) in the presence of excess tricine and stannous chloride to form the intermediate complex [99mTc(HYNIC-dimer)(tricine)2], which was then allowed to react with EDDA to afford [99mTc(HYNIC-dimer)(EDDA)] with high yield (>90%) and high specific activity ( approximately 8.0 Ci/micromol). Under the same radiolabeling conditions, the yield for [99mTc(HYNIC-tetramer)(EDDA)] was always EDDA bonding to the 99mTc-HYNIC core in [99mTc(HYNIC-dimer)(EDDA)]. The athymic nude mice bearing subcutaneous U87MG human glioma xenografts were used to evaluate the impact of EDDA coligand on the biodistribution characteristics and excretion kinetics of the 99mTc-labeled HYNIC-dimer and HYNIC-tetramer. Surprisingly, [99mTc(HYNIC-dimer)(EDDA)] and [99mTc(HYNIC-tetramer)(EDDA)] had almost identical tumor uptake over the 2 h period. The use of EDDA as coligand to replace tricine/TPPTS (TPPTS = trisodium triphenylphosphine-3,3',3''-trisulfonate) did not significantly change the uptake of the 99mTc-labeled HYNIC-dimer in noncancerous organs, such as the liver, kidneys, and lungs; but it did result in a significantly lower kidney uptake for the 99mTc-labeled HYNIC-tetramer due to faster renal excretion. It was also found that the radiotracer tumor uptake decreases in a linear fashion as the tumor size increases. The smaller the tumors are, the higher the tumor uptake is regardless of the identity of radiotracer.

Structural basis for the cooperative DNA recognition by Smad4 MH1 dimers

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Baburajendran, Nithya; Jauch, Ralf; Tan, Clara Yueh Zhen; Narasimhan, Kamesh; Kolatkar, Prasanna R.

2011-01-01

Smad proteins form multimeric complexes consisting of the ‘common partner’ Smad4 and receptor regulated R-Smads on clustered DNA binding sites. Deciphering how pathway specific Smad complexes multimerize on DNA to regulate gene expression is critical for a better understanding of the cis-regulatory logic of TGF-β and BMP signaling. To this end, we solved the crystal structure of the dimeric Smad4 MH1 domain bound to a palindromic Smad binding element. Surprisingly, the Smad4 MH1 forms a constitutive dimer on the SBE DNA without exhibiting any direct protein–protein interactions suggesting a DNA mediated indirect readout mechanism. However, the R-Smads Smad1, Smad2 and Smad3 homodimerize with substantially decreased efficiency despite pronounced structural similarities to Smad4. Therefore, intricate variations in the DNA structure induced by different Smads and/or variant energetic profiles likely contribute to their propensity to dimerize on DNA. Indeed, competitive binding assays revealed that the Smad4/R-Smad heterodimers predominate under equilibrium conditions while R-Smad homodimers are least favored. Together, we present the structural basis for DNA recognition by Smad4 and demonstrate that Smad4 constitutively homo- and heterodimerizes on DNA in contrast to its R-Smad partner proteins by a mechanism independent of direct protein contacts. PMID:21724602

UV-light exposure of insulin: pharmaceutical implications upon covalent insulin dityrosine dimerization and disulphide bond photolysis.

Science.gov (United States)

Correia, Manuel; Neves-Petersen, Maria Teresa; Jeppesen, Per Bendix; Gregersen, Søren; Petersen, Steffen B

2012-01-01

In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2)) excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin's structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes in protein

UV-light exposure of insulin: pharmaceutical implications upon covalent insulin dityrosine dimerization and disulphide bond photolysis.

Directory of Open Access Journals (Sweden)

Manuel Correia

Full Text Available In this work we report the effects of continuous UV-light (276 nm, ~2.20 W.m(-2 excitation of human insulin on its absorption and fluorescence properties, structure and functionality. Continuous UV-excitation of the peptide hormone in solution leads to the progressive formation of tyrosine photo-product dityrosine, formed upon tyrosine radical cross-linkage. Absorbance, fluorescence emission and excitation data confirm dityrosine formation, leading to covalent insulin dimerization. Furthermore, UV-excitation of insulin induces disulphide bridge breakage. Near- and far-UV-CD spectroscopy shows that UV-excitation of insulin induces secondary and tertiary structure losses. In native insulin, the A and B chains are held together by two disulphide bridges. Disruption of either of these bonds is likely to affect insulin's structure. The UV-light induced structural changes impair its antibody binding capability and in vitro hormonal function. After 1.5 and 3.5 h of 276 nm excitation there is a 33.7% and 62.1% decrease in concentration of insulin recognized by guinea pig anti-insulin antibodies, respectively. Glucose uptake by human skeletal muscle cells decreases 61.7% when the cells are incubated with pre UV-illuminated insulin during 1.5 h. The observations presented in this work highlight the importance of protecting insulin and other drugs from UV-light exposure, which is of outmost relevance to the pharmaceutical industry. Several drug formulations containing insulin in hexameric, dimeric and monomeric forms can be exposed to natural and artificial UV-light during their production, packaging, storage or administration phases. We can estimate that direct long-term exposure of insulin to sunlight and common light sources for indoors lighting and UV-sterilization in industries can be sufficient to induce irreversible changes to human insulin structure. Routine fluorescence and absorption measurements in laboratory experiments may also induce changes

Structural model and excitonic properties of the dimeric RC-LH1-PufX complex from Rhodobacter sphaeroides

International Nuclear Information System (INIS)

Sener, Melih; Hsin, Jen; Trabuco, Leonardo G.; Villa, Elizabeth; Qian, Pu; Hunter, C. Neil; Schulten, Klaus

2009-01-01

The light-harvesting apparatus of the purple bacterial photosynthetic unit consists of a pool of peripheral light-harvesting complexes that transfer excitation energy to a reaction center (RC) via the surrounding pigment-protein complex LH1. Recent electron microscopy and atomic force microscopy studies have revealed that RC-LH1 units of Rhodobacter (Rba.) sphaeroides form membrane-bending dimeric complexes together with the polypeptide PufX. We present a structural model for these RC-LH1-PufX dimeric complexes constructed using the molecular dynamics flexible fitting method based on an EM density map. The arrangement of the LH1 BChls displays a distortion near the proposed location of the PufX polypeptide. The resulting atomic model for BChl arrays is used to compute the excitonic properties of the dimeric RC-LH1 complex. A comparison is presented between the structural and excitonic features of the S-shaped dimeric BChl array of Rba. sphaeroides and the circular BChl arrangement found in other purple bacteria

Revealing the Dimeric Crystal and Solution Structure of β-Lactoglobulin at pH 4 and Its pH and Salt Dependent Monomer–Dimer Equilibrium

DEFF Research Database (Denmark)

Khan, Sanaullah; Ipsen, Richard; Almdal, Kristoffer

2018-01-01

The dimeric structure of bovine β-lactoglobulin A (BLGA) at pH 4.0 was solved to 2.0 Å resolution. Fitting the BLGA pH 4.0 structure to SAXS data at low ionic strength (goodness of fit R-factor = 3.6%) verified the dimeric state in solution. Analysis of the monomer–dimer equilibrium at varying pH...... and ionic strength by SAXS and scattering modeling showed that BLGA is dimeric at pH 3.0 and 4.0, shifting toward a monomer at pH 2.2, 2.6, and 7.0 yielding monomer/dimer ratios of 80/20%, 50/50%, and 25/75%, respectively. BLGA remained a dimer at pH 3.0 and 4.0 in 50–150 mM NaCl, whereas the electrostatic...... shielding raised the dimer content at pH 2.2, 2.6, and 7.0, i.e., below and above the pI. Overall, the findings provide new insights into the molecular characteristics of BLGA relevant for dairy product formulations and for various biotechnological and pharmaceutical applications....

L-Cysteine halogenides: A new family of salts with an L-cysteine⋯L-cysteinium dimeric cation

Science.gov (United States)

Ghazaryan, V. V.; Minkov, V. S.; Boldyreva, E. V.; Petrosyan, A. M.

2016-10-01

Two L-cysteinium-halogenides with (L-cysteine···L-cysteinium) dimeric cations have been obtained, (L-Cys⋯L-Cys+)·Cl-, and (L-Cys⋯L-Cys+)·Br-. Both salts crystallize in monoclinic space group P21. Although these salts have the same dimeric cations and isotypical halogen anions, crystal packing is different. The main difference between the two salts rests in the conformation of (L-Cys⋯L-Cys+) dimeric cation, which also differs from that of the dimeric cation in the previously reported compound L-Cys+(L-Cys⋯L-Cys+)·F-·(F-⋯HF). The dimeric cation is formed by a very short O-H⋯O hydrogen bond with d(O···O) of 2.449(2) Å and 2.435(11) Å in the chloride and bromide, respectively. In addition to crystal structure analysis, Infrared and Raman spectra have been registered and discussed with a particular focus on intermolecular interactions. The L-Cys+·Br-·H2O salt with a simple L-cysteinium cation was also obtained and the crystal structure solved. It resembles its chloride analogue, L-Cys+·Cl-·H2O.

Renormalization group analysis of B →π form factors with B -meson light-cone sum rules

Science.gov (United States)

Shen, Yue-Long; Wei, Yan-Bing; Lü, Cai-Dian

2018-03-01

Within the framework of the B -meson light-cone sum rules, we review the calculation of radiative corrections to the three B →π transition form factors at leading power in Λ /mb. To resum large logarithmic terms, we perform the complete renormalization group evolution of the correlation function. We employ the integral transformation which diagonalizes evolution equations of the jet function and the B -meson light-cone distribution amplitude to solve these evolution equations and obtain renormalization group improved sum rules for the B →π form factors. Results of the form factors are extrapolated to the whole physical q2 region and are compared with that of other approaches. The effect of B -meson three-particle light-cone distribution amplitudes, which will contribute to the form factors at next-to-leading power in Λ /mb at tree level, is not considered in this paper.

Crystal Structure of Ripk4 Reveals Dimerization-Dependent Kinase Activity.

Science.gov (United States)

Huang, Christine S; Oberbeck, Nina; Hsiao, Yi-Chun; Liu, Peter; Johnson, Adam R; Dixit, Vishva M; Hymowitz, Sarah G

2018-05-01

Receptor-interacting protein kinase 4 (RIPK4) is a highly conserved regulator of epidermal differentiation. Members of the RIPK family possess a common kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences. Mutations in human RIPK4 manifest as Bartsocas-Papas syndrome (BPS), a genetic disorder characterized by severe craniofacial and limb abnormalities. We describe the structure of the murine Ripk4 (MmRipk4) kinase domain, in ATP- and inhibitor-bound forms. The crystallographic dimer of MmRipk4 is similar to those of RIPK2 and BRAF, and we show that the intact dimeric entity is required for MmRipk4 catalytic activity through a series of engineered mutations and cell-based assays. We also assess the impact of BPS mutations on protein structure and activity to elucidate the molecular origins of the disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

Determination of the Tetramer-Dimer Equilibrium Constant of Rabbit ...

African Journals Online (AJOL)

Hemoglobin is a tetrameric protein which is able to dissociate into dimers. The dimers can in turn dissociate into tetramers. It has been found that dimers are more reactive than tetramers. The difference in the reactivity of these two species has been used to determine the tetramerdimer dissociation constant of various ...

Viscosity and sedimentation behaviors of the magnetorheological suspensions with oleic acid/dimer acid as surfactants

Science.gov (United States)

Yang, Jianjian; Yan, Hua; Hu, Zhide; Ding, Ding

2016-11-01

This work deals with the role of polar interactions on the viscosity and sedimentation behaviors of magnetorheological suspensions with micro-sized magnetic particles dispersed in oil carriers. The oleic acid and dimer acid were employed to make an adjustment of the hydrophobicity of iron particles, in the interest of performing a comparative evaluation of the contributions of the surface polarity. The viscosity tests show that the adsorbed surfactant layer may impose a hindrance to the movement of iron particles in the oil medium. The polar attractions between dimer acid covered particles gave rise to a considerable increase in viscosity, indicating flocculation structure developed in the suspensions. The observed plateau-like region in the vicinity of 0.1 s-1 for MRF containing dimer acid is possibly due to the flocculation provoked by the carboxylic polar attraction, in which the structure is stable against fragmentation. Moreover, a quick recovery of the viscosity and a higher viscosity-temperature index also suggest the existence of particle-particle polar interaction in the suspensions containing dimer acid. The sedimentation measurements reveal that the steric repulsion of oleic acid plays a limited role in the stability of suspensions only if a large quantity of surfactant was used. The sedimentation results observed in the dimer acid covered particles confirm that loose and open flocculation was formed and enhanced sedimentation stability.

Structural basis underlying CAC RNA recognition by the RRM domain of dimeric RNA-binding protein RBPMS

Energy Technology Data Exchange (ETDEWEB)

Teplova, Marianna; Farazi, Thalia A.; Tuschl, Thomas; Patel, Dinshaw J.

2015-09-08

RNA-binding protein with multiple splicing (designated RBPMS) is a higher vertebrate mRNA-binding protein containing a single RNA recognition motif (RRM). RBPMS has been shown to be involved in mRNA transport, localization and stability, with key roles in axon guidance, smooth muscle plasticity, as well as regulation of cancer cell proliferation and migration. We report on structure-function studies of the RRM domain of RBPMS bound to a CAC-containing single-stranded RNA. These results provide insights into potential topologies of complexes formed by the RBPMS RRM domain and the tandem CAC repeat binding sites as detected by photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation. These studies establish that the RRM domain of RBPMS forms a symmetrical dimer in the free state, with each monomer binding sequence-specifically to all three nucleotides of a CAC segment in the RNA bound state. Structure-guided mutations within the dimerization and RNA-binding interfaces of RBPMS RRM on RNA complex formation resulted in both disruption of dimerization and a decrease in RNA-binding affinity as observed by size exclusion chromatography and isothermal titration calorimetry. As anticipated from biochemical binding studies, over-expression of dimerization or RNA-binding mutants of Flag-HA-tagged RBPMS were no longer able to track with stress granules in HEK293 cells, thereby documenting the deleterious effects of such mutationsin vivo.

The synthetic epoxyquinoids jesterone dimer and epoxyquinone A monomer induce apoptosis and inhibit REL (human c-Rel) DNA binding in an IkappaBalpha-deficient diffuse large B-cell lymphoma cell line.

Science.gov (United States)

Liang, Mei-Chih; Bardhan, Sujata; Porco, John A; Gilmore, Thomas D

2006-09-08

The NF-kappaB transcription factor signaling pathway is constitutively active in many human cancers, and inhibition of this pathway can often kill cancer cells by inducing apoptosis. In this study, we show that two synthetic epoxyquinoids, jesterone dimer (JD) and epoxyquinone A monomer (EqM), are equally effective at inhibiting the growth of two human lymphoma cell lines that have constitutively nuclear REL (human c-Rel) DNA-binding complexes, but either express (SUDHL-4 cells) or do not express (RC-K8 cells) the NF-kappaB inhibitor IkappaBalpha. Furthermore, in these cells, both JD and EqM dose-dependently induced apoptosis, inhibited REL DNA-binding activity, and converted REL to a high molecular weight form. In A293 cells, JD and EqM inhibited the DNA-binding activity of overexpressed REL, but not p50. Replacement of Cys-27 with Ser in REL reduced JD- and EqM-mediated inhibition of REL DNA-binding activity. These results suggest that JD and EqM can induce apoptosis in IkappaBalpha-deficient lymphoma cells through a mechanism involving direct inhibition of transcription factor REL.

Spectroscopic investigation on structure (monomer and dimer), molecular characteristics and comparative study on vibrational analysis of picolinic and isonicotinic acids using experimental and theoretical (DFT & IVP) methods

Science.gov (United States)

Ramesh, Gaddam; Reddy, Byru Venkatram

2018-05-01

In this investigation, the monomeric structure is determined for picolinic and isonicotinic acids based on geometry optimization for one of the four possible conformers and intramolecular hydrogen bond of Osbnd H⋯O using density functional theory (DFT) employing B3LYP functional supplemented with 6-311++G(d,p) basis set. Using this optimized monomeric form, the dimer structure is determined based on minimum energy and length of hydrogen bonds obtained for two possible dimeric forms yielded due to head-to-tail intermolecular Osbnd H⋯N hydrogen bond (dimer 1) linkage and tail-to -tail intermolecular Osbnd H⋯O hydrogen bond (dimer 2) linkage between pyridine ring and carboxyl group. The structure parameters obtained for monomer and dimer forms are in good agreement with the experimental literature values. The vibrational assignments have been made unambiguously for all the vibrations from FTIR and FT-Raman spectra based on the potential energy distribution (PED) and eigen vectors obtained in DFT and inverse vibrational problem (IVP) computations. The rms error between the observed and scaled frequencies is 7.7 and 9.4 cm-1 for PIA and INA, respectively. A 74-element modified valence force field is derived by Wilson's GF matrix method using 58 experimental frequencies of the two molecules in overlay least-squares technique. The average error between observed and computed frequencies by this method is calculated to be 10.39 cm-1. The results of both DFT and IVP computations yielded good agreement between observed and calculated frequencies. The NLO behaviour using hyperpolarizability values; and HOMO and LUMO energies; of the two molecules are investigated by DFT. Charge density distribution and site of chemical reactivity of the molecules are studied by molecular electrostatic surface potential (MESP). Stability of the molecules arising from hyper conjugative interactions and charge delocalization has been analyzed using natural bond orbital (NBO

Perturbative corrections to B → D form factors in QCD

Science.gov (United States)

Wang, Yu-Ming; Wei, Yan-Bing; Shen, Yue-Long; Lü, Cai-Dian

2017-06-01

We compute perturbative QCD corrections to B → D form factors at leading power in Λ/ m b , at large hadronic recoil, from the light-cone sum rules (LCSR) with B-meson distribution amplitudes in HQET. QCD factorization for the vacuum-to- B-meson correlation function with an interpolating current for the D-meson is demonstrated explicitly at one loop with the power counting scheme {m}_c˜ O(√{Λ {m}_b}) . The jet functions encoding information of the hard-collinear dynamics in the above-mentioned correlation function are complicated by the appearance of an additional hard-collinear scale m c , compared to the counterparts entering the factorization formula of the vacuum-to- B-meson correction function for the construction of B → π from factors. Inspecting the next-to-leading-logarithmic sum rules for the form factors of B → Dℓν indicates that perturbative corrections to the hard-collinear functions are more profound than that for the hard functions, with the default theory inputs, in the physical kinematic region. We further compute the subleading power correction induced by the three-particle quark-gluon distribution amplitudes of the B-meson at tree level employing the background gluon field approach. The LCSR predictions for the semileptonic B → Dℓν form factors are then extrapolated to the entire kinematic region with the z-series parametrization. Phenomenological implications of our determinations for the form factors f BD +,0 ( q 2) are explored by investigating the (differential) branching fractions and the R( D) ratio of B → Dℓν and by determining the CKM matrix element |V cb | from the total decay rate of B → Dμν μ .

Dualism of Sensitivity and Selectivity of Porphyrin Dimers in Electroanalysis.

Science.gov (United States)

Lisak, Grzegorz; Tamaki, Takashi; Ogawa, Takuji

2017-04-04

This work uncovers the application of porphyrin dimers for the use in electroanalysis, such as potentiometric determination of ions. It also puts in question a current perception of an occurrence of the super-Nernstian response, as a result of the possible dimerization of single porphyrins within an ion-selective membrane. To study that, four various porphyrin dimers were used as ionophores, namely, freebase-freebase, Zn-Zn, Zn-freebase, and freebase-Zn. Since the Zn-freebase and freebase-Zn porphyrin dimers carried both anion- and cation-sensitive porphyrin units, their application in ISEs was utilized in both anion- and cation-sensitive sensors. With respect to the lipophilic salt added, both porphyrins dimers were found anion- and cation-sensitive. This allowed using a single molecule as novel type of versatile ionophore (anion- and cation-selective), simply by varying the membrane composition. All anion-sensitive sensors were perchlorate-sensitive, while the cation-selective sensors were silver-sensitive. The selectivity of the sensors depended primarily on the porphyrin dimers in the ion-selective membrane. Furthermore, the selectivity of cation-sensitive dimer based sensors was found significantly superior to the ones measured for the single porphyrin unit based sensors (precursors of the porphyrin dimers). Thus, the dimerization of single porphyrins may actually be a factor to increase or modulate porphyrin selectivity. Moreover, in the case of cation-sensitive sensors, the selectivity vastly depended on the order of porphyrin units in the dimer. This opens a new approach of regulating and adjusting sensitivity and selectivity of the sensor through the application of complex porphyrin systems with more than one porphyrin units with mix sensitive porphyrins.

Beta2-adrenergic receptor homodimers: Role of transmembrane domain 1 and helix 8 in dimerization and cell surface expression.

Science.gov (United States)

Parmar, Vikas K; Grinde, Ellinor; Mazurkiewicz, Joseph E; Herrick-Davis, Katharine

2017-09-01

Even though there are hundreds of reports in the published literature supporting the hypothesis that G protein-coupled receptors (GPCR) form and function as dimers this remains a highly controversial area of research and mechanisms governing homodimer formation are poorly understood. Crystal structures revealing homodimers have been reported for many different GPCR. For adrenergic receptors, a potential dimer interface involving transmembrane domain 1 (TMD1) and helix 8 (H8) was identified in crystal structures of the beta 1 -adrenergic (β 1 -AR) and β 2 -AR. The purpose of this study was to investigate a potential role for TMD1 and H8 in dimerization and plasma membrane expression of functional β 2 -AR. Charged residues at the base of TMD1 and in the distal portion of H8 were replaced, singly and in combination, with non-polar residues or residues of opposite charge. Wild type and mutant β 2 -AR, tagged with YFP and expressed in HEK293 cells, were evaluated for plasma membrane expression and function. Homodimer formation was evaluated using bioluminescence resonance energy transfer, bimolecular fluorescence complementation, and fluorescence correlation spectroscopy. Amino acid substitutions at the base of TMD1 and in the distal portion of H8 disrupted homodimer formation and caused receptors to be retained in the endoplasmic reticulum. Mutations in the proximal region of H8 did not disrupt dimerization but did interfere with plasma membrane expression. This study provides biophysical evidence linking a potential TMD1/H8 interface with ER export and the expression of functional β 2 -AR on the plasma membrane. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova. Copyright © 2016 Elsevier B.V. All rights reserved.

Factors associated with D-dimer levels in HIV-infected individuals

DEFF Research Database (Denmark)

Borges, Alvaro H; O'Connor, Jemma L; Phillips, Andrew N

2014-01-01

BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. METHODS: In this cross-sectional study, participants in three randomized controlled trials...... with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6...... viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high...

Mechanism for Controlling the Dimer-Monomer Switch and Coupling Dimerization to Catalysis of the Severe Acute Respiratory Syndrome Coronavirus 3C-Like Protease

Energy Technology Data Exchange (ETDEWEB)

Shi,J.; Sivaraman, J.; Song, J.

2008-01-01

Unlike 3C protease, the severe acute respiratory syndrome coronavirus (SARS-CoV) 3C-like protease (3CLpro) is only enzymatically active as a homodimer and its catalysis is under extensive regulation by the unique extra domain. Despite intense studies, two puzzles still remain: (i) how the dimer-monomer switch is controlled and (ii) why dimerization is absolutely required for catalysis. Here we report the monomeric crystal structure of the SARS-CoV 3CLpro mutant R298A at a resolution of 1.75 Angstroms . Detailed analysis reveals that Arg298 serves as a key component for maintaining dimerization, and consequently, its mutation will trigger a cooperative switch from a dimer to a monomer. The monomeric enzyme is irreversibly inactivated because its catalytic machinery is frozen in the collapsed state, characteristic of the formation of a short 310-helix from an active-site loop. Remarkably, dimerization appears to be coupled to catalysis in 3CLpro through the use of overlapped residues for two networks, one for dimerization and another for the catalysis.

A structural model of the E. coli PhoB Dimer in the transcription initiation complex

Directory of Open Access Journals (Sweden)

Tung Chang-Shung

2012-03-01

Full Text Available Abstract Background There exist > 78,000 proteins and/or nucleic acids structures that were determined experimentally. Only a small portion of these structures corresponds to those of protein complexes. While homology modeling is able to exploit knowledge-based potentials of side-chain rotomers and backbone motifs to infer structures for new proteins, no such general method exists to extend our understanding of protein interaction motifs to novel protein complexes. Results We use a Motif Binding Geometries (MBG approach, to infer the structure of a protein complex from the database of complexes of homologous proteins taken from other contexts (such as the helix-turn-helix motif binding double stranded DNA, and demonstrate its utility on one of the more important regulatory complexes in biology, that of the RNA polymerase initiating transcription under conditions of phosphate starvation. The modeled PhoB/RNAP/σ-factor/DNA complex is stereo-chemically reasonable, has sufficient interfacial Solvent Excluded Surface Areas (SESAs to provide adequate binding strength, is physically meaningful for transcription regulation, and is consistent with a variety of known experimental constraints. Conclusions Based on a straightforward and easy to comprehend concept, "proteins and protein domains that fold similarly could interact similarly", a structural model of the PhoB dimer in the transcription initiation complex has been developed. This approach could be extended to enable structural modeling and prediction of other bio-molecular complexes. Just as models of individual proteins provide insight into molecular recognition, catalytic mechanism, and substrate specificity, models of protein complexes will provide understanding into the combinatorial rules of cellular regulation and signaling.

Phosphorous dimerization in GaP high-pressure polymorph

Energy Technology Data Exchange (ETDEWEB)

Lavina, Barbara [Univ. of Nevada, Las Vegas, NV (United States). High Pressure Science and Engineering Center (HiPSEC), Dept. of Physics and Astronomy; Kim, Eunja [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Physics and Astronomy; Cynn, Hyunchae [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Weck, Philippe F [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Seaborg, Kelly [Univ. of Nevada, Las Vegas, NV (United States). High Pressure Science and Engineering Center (HiPSEC), Dept. of Physics and Astronomy; Siska, Emily [Univ. of Nevada, Las Vegas, NV (United States). High Pressure Science and Engineering Center (HiPSEC); Meng, Yue [Carnegie Inst. of Washington, Argonne, IL (United States). Geophysical Lab., High Pressure Collaborative Access Team (HPCAT); Evans, Williams [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

2016-06-01

We report on the experimental and theoretical characterization of a novel GaP polymorph formed by laser heating of a single crystal of GaP-II in its stable region near 43 GPa. Thereby formed unstrained multigrain sample at 43 GPa and 1300 K, allowed high-resolution crystallographic analysis. We find an oS24 as an energetically optimized crystal structure contrary to oS8 reported by Nelmes et al. (1997). Our DFT calculation confirms a stable existence of oS24 between 18 – 50 GPa. The emergence of the oS24 structure is related to the differentiation of phosphorous atoms between those forming P-P dimers and those forming P-Ga bonds only. Bonding anisotropy explains the symmetry lowering with respect to what is generally expected for semiconductors high-pressure polymorphs. The metallization of GaP does not occur through a uniform change of the nature of its bonds but through the formation of an anisotropic phase containing different bond types.

Evaluation of DFT methods for computing the interaction energies of homomolecular and heteromolecular dimers of monosubstituted benzene

Science.gov (United States)

Godfrey-Kittle, Andrew; Cafiero, Mauricio

We present density functional theory (DFT) interaction energies for the sandwich and T-shaped conformers of substituted benzene dimers. The DFT functionals studied include TPSS, HCTH407, B3LYP, and X3LYP. We also include Hartree-Fock (HF) and second-order Møller-Plesset perturbation theory calculations (MP2), as well as calculations using a new functional, P3LYP, which includes PBE and HF exchange and LYP correlation. Although DFT methods do not explicitly account for the dispersion interactions important in the benzene-dimer interactions, we find that our new method, P3LYP, as well as HCTH407 and TPSS, match MP2 and CCSD(T) calculations much better than the hybrid methods B3LYP and X3LYP methods do.

Surface damage in cystine, an amino acid dimer, induced by keV ions.

Science.gov (United States)

Salles, R C M; Coutinho, L H; da Veiga, A G; Sant'Anna, M M; de Souza, G G B

2018-01-28

We have studied the interaction of an ion beam (17.6 keV F - ) with cystine, a dimer formed by the binding of two cysteine residues. Cystine can be considered as an ideal prototype for the study of the relevance of the disulfide (-S-S-) chemical bond in biomolecules. For the sake of comparison, the amino acid cysteine has also been subjected to the same experimental conditions. Characterization of the samples by XPS and NEXAFS shows that both pristine cystine and pristine cysteine are found as a dipolar ion (zwitterion). Following irradiation, the dimer and the amino acid show a tendency to change from the dipole ion form to the normal uncharged form. The largest spectral modification was observed in the high resolution XPS spectra obtained at around the N 1s core level for the two biomolecules. The 2p sulfur edge spectra of cysteine and cystine were much less sensitive to radiation effects. We suggest that the disulfide bond (-S-S-) remains stable before and after irradiation, contributing to the larger radiation stability of cystine as compared to the amino acid cysteine.

Modeling the structure and vibrational spectra for oxouranium dichloride monomer and dimer

Science.gov (United States)

Umreiko, D. S.; Shundalau, M. B.; Trubina, O. V.

2010-11-01

Structural models are designed and spectral characteristics are computed for the monomer and dimer of the oxouranium dichloride (UOCl2) molecule based on ab initio calculations. The calculations were carried out in the LANL2DZ effective core potential approximation for the uranium atom and all-electron basis sets using DFT methods for oxygen and chlorine atoms (B3LYP/cc-pVDZ). A close-to-planar Y-shaped equilibrium configuration with Cs symmetry is obtained for the UOCl2 monomer. The formation of the dimer is accompanied by both significant changes in the structure of the monomeric fragments and the actual loss of their identities. The obtained spectral characteristics are analyzed and compared with experimental data. The adequacy of the proposed models and qualitative agreement between calculation and experiment are demonstrated.

A new hydroxychavicol dimer from the roots of Piper betle.

Science.gov (United States)

Lin, Chwan-Fwu; Hwang, Tsong-Long; Chien, Chun-Chien; Tu, Huei-Yu; Lay, Horng-Liang

2013-02-26

A new hydroxychavicol dimer, 2-(g'-hydroxychavicol)-hydroxychavicol (1), was isolated from the roots of Piper betle Linn. along with five known compounds, hydroxychavicol (2), aristololactam A II (3), aristololactam B II (4), piperolactam A (5) and cepharadione A (6). The structures of these isolated compounds were elucidated by spectroscopic methods. Compounds 1 and 2 exhibited inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.

A New Hydroxychavicol Dimer from the Roots of Piper betle

Directory of Open Access Journals (Sweden)

Huei-Yu Tu

2013-02-01

Full Text Available A new hydroxychavicol dimer, 2-(g'-hydroxychavicol-hydroxychavicol (1, was isolated from the roots of Piper betle Linn. along with five known compounds, hydroxychavicol (2, aristololactam A II (3, aristololactam B II (4, piperolactam A (5 and cepharadione A (6. The structures of these isolated compounds were elucidated by spectroscopic methods. Compounds 1 and 2 exhibited inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils.

Ultrafast deactivation processes in the 2-aminopyridine dimer and the adenine-thymine base pair: Similarities and differences

International Nuclear Information System (INIS)

Ai Yuejie; Zhang Feng; Cui Ganglong; Fang Weihai; Luo Yi

2010-01-01

2-aminopyridine dimer has frequently been used as a model system for studying photochemistry of DNA base pairs. We examine here the relevance of 2-aminopyridine dimer for a Watson-Crick adenine-thymine base pair by studying UV-light induced photodynamics along two main hydrogen bridges after the excitation to the localized 1 ππ* excited-state. The respective two-dimensional potential-energy surfaces have been determined by time-dependent density functional theory with Coulomb-attenuated hybrid exchange-correlation functional (CAM-B3LYP). Different mechanistic aspects of the deactivation pathway have been analyzed and compared in detail for both systems, while the related reaction rates have also be obtained from Monte Carlo kinetic simulations. The limitations of the 2-aminopyridine dimer as a model system for the adenine-thymine base pair are discussed.

Conformational stability of the epidermal growth factor (EGF) receptor as influenced by glycosylation, dimerization and EGF hormone binding.

Science.gov (United States)

Taylor, Eric S; Pol-Fachin, Laercio; Lins, Roberto D; Lower, Steven K

2017-04-01

The epidermal growth factor receptor (EGFR) is an important transmembrane glycoprotein kinase involved the initiation or perpetuation of signal transduction cascades within cells. These processes occur after EGFR binds to a ligand [epidermal growth factor (EGF)], thus inducing its dimerization and tyrosine autophosphorylation. Previous publications have highlighted the importance of glycosylation and dimerization for promoting proper function of the receptor and conformation in membranes; however, the effects of these associations on the protein conformational stability have not yet been described. Molecular dynamics simulations were performed to characterize the conformational preferences of the monomeric and dimeric forms of the EGFR extracellular domain upon binding to EGF in the presence and absence of N-glycan moieties. Structural stability analyses revealed that EGF provides the most conformational stability to EGFR, followed by glycosylation and dimerization, respectively. The findings also support that EGF-EGFR binding takes place through a large-scale induced-fitting mechanism. Proteins 2017; 85:561-570. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Microstructural analysis of hot press formed 22MnB5 steel

Science.gov (United States)

Aziz, Nuraini; Aqida, Syarifah Nur; Ismail, Izwan

2017-10-01

This paper presents a microstructural study on hot press formed 22MnB5 steel for enhanced mechanical properties. Hot press forming process consists of simultaneous forming and quenching of heated blank. The 22MnB5 steel was processed at three different parameter settings: quenching time, water temperature and water flow rate. 22MnB5 was processed using 33 full factorial design of experiment (DOE). The full factorial DOE was designed using three factors of quenching time, water temperature and water flow rate at three levels. The factors level were quenching time range of 5 - 11 s, water temperature; 5 - 27°C and water flow rate; 20 - 40 L/min. The as-received and hot press forming processed steel was characterised for metallographic study and martensitic structure area percentage using JEOL Field Emission Scanning Electron Microscopic (FESEM). From the experimental finding, the hot press formed 22MnB5 steel consisted of 50 to 84% martensitic structure area. The minimum quenching time of 8 seconds was required to obtain formed sample with high percentage of martensite. These findings contribute to initial design of processing parameters in hot press forming of 22MnB5 steel blanks for automotive component.

Association of atoms into universal dimers using an oscillating magnetic field.

Science.gov (United States)

Langmack, Christian; Smith, D Hudson; Braaten, Eric

2015-03-13

In a system of ultracold atoms near a Feshbach resonance, pairs of atoms can be associated into universal dimers by an oscillating magnetic field with a frequency near that determined by the dimer binding energy. We present a simple expression for the transition rate that takes into account many-body effects through a transition matrix element of the contact. In a thermal gas, the width of the peak in the transition rate as a function of the frequency is determined by the temperature. In a dilute Bose-Einstein condensate of atoms, the width is determined by the inelastic scattering rates of a dimer with zero-energy atoms. Near an atom-dimer resonance, there is a dramatic increase in the width from inelastic atom-dimer scattering and from atom-atom-dimer recombination. The recombination contribution provides a signature for universal tetramers that are Efimov states consisting of two atoms and a dimer.

Efficient photosensitized splitting of the thymine dimer/oxetane unit on its modifying beta-cyclodextrin by a binding electron donor.

Science.gov (United States)

Tang, Wen-Jian; Song, Qin-Hua; Wang, Hong-Bo; Yu, Jing-Yu; Guo, Qing-Xiang

2006-07-07

Two modified beta-cyclodextrins (beta-CDs) with a thymine dimer and a thymine oxetane adduct respectively, TD-CD and Ox-CD, have been prepared, and utilized to bind an electron-rich chromophore, indole or N,N-dimethylaniline (DMA), to form a supramolecular complex. We have examined the photosensitized splitting of the dimer/oxetane unit in TD-CD/Ox-CD by indole or DMA via an electron-transfer pathway, and observed high splitting efficiencies of the dimer/oxetane unit. On the basis of measurements of fluorescence spectra and splitting quantum yields, it is suggested that the splitting reaction occurs in a supramolecular complex by an inclusion interaction between the modified beta-CDs and DMA or indole. The back electron transfer, which leads low splitting efficiencies for the covalently-linked chromophore-dimer/oxetane compounds, is suppressed in the non-covalently-bound complex, and the mechanism has been discussed.

Structures of DNA containing psoralen crosslink and thymine dimer

International Nuclear Information System (INIS)

Kim, S.H.; Pearlman, D.A.; Holbrook, S.R.; Pirkle, D.

1985-01-01

UV irradiation by itself or in conjunction with other chemicals can cause covalent damages to DNA in living cells. To overcome the detrimental effect of DNA damage, cells developed a repair mechanism by which damaged DNA is repaired. In the absence of such repair, cell malfunction or cell death can occur. Two most studied radiation-induced DNA damage are thymine dimer formation by UV irradiation and psoralen crosslink by combination of psoralens and UV: In the former, two adjacent thymine bases on a strand of DNA are fused by forming cyclobutane ring, and in the latter, one pyrimidine on one DNA strand is crosslinked to another pyrimidine on the other strand via a psoralen. The authors' objective is to deduce the structure of DNA segment which contains a psoralen crosslink or a thymine dimer using the combination of results of X-ray crystallographic studies, molecular model building, and energy minimization. These structural features may be important for understanding the biological effects of such damages and for the recognition by the repair enzymes

The Structure of the Poxvirus A33 Protein Reveals a Dimer of Unique C-Type Lectin-Like Domains

Energy Technology Data Exchange (ETDEWEB)

Su, Hua-Poo; Singh, Kavita; Gittis, Apostolos G.; Garboczi, David N. (NIH)

2010-11-03

The current vaccine against smallpox is an infectious form of vaccinia virus that has significant side effects. Alternative vaccine approaches using recombinant viral proteins are being developed. A target of subunit vaccine strategies is the poxvirus protein A33, a conserved protein in the Chordopoxvirinae subfamily of Poxviridae that is expressed on the outer viral envelope. Here we have determined the structure of the A33 ectodomain of vaccinia virus. The structure revealed C-type lectin-like domains (CTLDs) that occur as dimers in A33 crystals with five different crystal lattices. Comparison of the A33 dimer models shows that the A33 monomers have a degree of flexibility in position within the dimer. Structural comparisons show that the A33 monomer is a close match to the Link module class of CTLDs but that the A33 dimer is most similar to the natural killer (NK)-cell receptor class of CTLDs. Structural data on Link modules and NK-cell receptor-ligand complexes suggest a surface of A33 that could interact with viral or host ligands. The dimer interface is well conserved in all known A33 sequences, indicating an important role for the A33 dimer. The structure indicates how previously described A33 mutations disrupt protein folding and locates the positions of N-linked glycosylations and the epitope of a protective antibody.

Dimers of fluorinated methanes with carbonyl sulfide: the rotational spectrum and structure of difluoromethane-OCS.

Science.gov (United States)

Serafin, Michal M; Peebles, Sean A

2008-12-11

The pure rotational spectra of four isotopologues of the difluoromethane-carbonyl sulfide dimer have been measured in the 5-15 GHz region with use of pulsed-nozzle Fourier-transform microwave spectroscopy. The complex was determined to possess an ab plane of symmetry with a center of mass separation of 3.41(2) A and dipole moment components mu(a) = 1.1386(18) D, mu(b) = 0.4840(63) D, mu(total) = 1.2372(41) D. Experimental planar moments indicate that the two fluorine atoms straddle the symmetry plane while one of the C-H bonds of the difluoromethane monomer is aligned to interact with the oxygen atom of the OCS molecule. The assignment of the rotational spectrum for this dimer completes the experimental studies of the series of dimers involving fluorinated methanes (HCF(3), H(2)CF(2), and H(3)CF) complexed with OCS and makes possible a comparison of properties within this series.

Kinetics of thymine dimer excision in ultraviolet-irradiated human cells

International Nuclear Information System (INIS)

Ehmann, U.K.; Cook, K.H.; Friedberg, E.C.

1978-01-01

We have investigated the kinetics of the loss of thymine dimers from the acid-insoluble fraction of several ultraviolet (uv)-irradiated cultured human cell lines. Our results show that uv fluences between 10 and 40 J/m 2 produce an average of 21 to 85 x 10 5 thymine dimers per cell and an eventual maximal loss per cell of 12 to 20 x 10 5 thymine dimers. The time for half-maximal loss of dimers ranged from 12 to 22 h after uv irradiation. In contrast, the time for half-maximal repair synthesis of DNA measured by autoradiography was 4.5 h. This figure agrees well with reported half-maximal repair synthesis times, which range from 0.5 to 3.6 h based on our analysis. The discrepancy in the kinetics of the loss of thymine dimers from DNA and repair synthesis is discussed in terms of possible molecular mechanisms of thymine dimer excision in vivo and in terms of possible experimental artifacts

Role of cyclobutane dimers in UV-denaturation of DNA

International Nuclear Information System (INIS)

Zavil'gel'skij, G.B.; Zuev, A.V.

1978-01-01

UV irradiation of double-stranded DNA produces local denatured regions. The evidence presented indicates that these single-stranded regions arise from photoproducts other than pyrimidine dimers. The irradiation of T2 DNA at 8x10 4 erg/mm 2 (254 nm) produces 6-8% thymine dimers, amd Tsub(mel) drops by 12-14 deg C, accompanied by a significant broadening of the transition profile. The kinetics of denatured region formation and lowering Tsub(mel) corresponds to that of formation of crosslinkages and differs markedly from the kinetics of formation of cyclobutane pyrimidine dimers. Treatment of UV-irradiated DNA with light in the presence of yeast photoreactivating enzyme monomerizes almost all thymine dimers but does not change the Tsub(mel). Local denatured regions are detected in UV-irradiated DNA and are absent from AcPhM-sensibilized DNA, which contains 20-25% thymine dimers, as determined by the accridine orange fluorescence technique. S1 nuclease from Aspergillis oryzae produces single-strand breaks in UV-irradiated DNA of phage PM2 but is not active on AcPhM-treated PM2 DNA, which contains about 50 thymine dimers. It is supposed that the formation of a cyclobutane dimer only weakens the hydrogen bonds in the AT base pair rather than breaks them. Local denatured regions are thought to arise from the accumulation in UV-irradiated DNA (254 nm) of the sufficient number of photoproducts with impaired ability to base pairing

Characterization of oxygen dimer-enriched silicon detectors

CERN Document Server

Boisvert, V; Moll, M; Murin, L I; Pintilie, I

2005-01-01

Various types of silicon material and silicon p+n diodes have been treated to increase the concentration of the oxygen dimer (O2i) defect. This was done by exposing the bulk material and the diodes to 6 MeV electrons at a temperature of about 350 °C. FTIR spectroscopy has been performed on the processed material confirming the formation of oxygen dimer defects in Czochralski silicon pieces. We also show results from TSC characterization on processed diodes. Finally, we investigated the influence of the dimer enrichment process on the depletion voltage of silicon diodes and performed 24 GeV/c proton irradiations to study the evolution of the macroscopic diode characteristics as a function of fluence.

Dimeric Surfactants: Promising Ingredients of Cosmetics and Toiletries

Directory of Open Access Journals (Sweden)

Naveen Kumar

2013-11-01

Full Text Available Surfactants are an essential ingredient for cosmetic, toiletries and personal care products for enhancing their performance. Dimeric surfactants demonstrate superiority compared to conventional surfactants in all areas of application. Dimeric surfactants are extremely promising for utilization in various cosmetic formulations viz. shampoo, lotions, creams, conditioners etc. These surfactants possess extremely unique surface properties viz. lower surface tension, unique micellization, low critical micelle concentration (CMC and antimicrobial activity, higher solubilization etc. Dimerics enhance the performances of cosmetics in an extraordinary manner and provide eco-friendly preparations for human epidermis.

Sequential cancer immunotherapy: targeted activity of dimeric TNF and IL-8

Science.gov (United States)

Adrian, Nicole; Siebenborn, Uta; Fadle, Natalie; Plesko, Margarita; Fischer, Eliane; Wüest, Thomas; Stenner, Frank; Mertens, Joachim C.; Knuth, Alexander; Ritter, Gerd; Old, Lloyd J.; Renner, Christoph

2009-01-01

Polymorphonuclear neutrophils (PMNs) are potent effectors of inflammation and their attempts to respond to cancer are suggested by their systemic, regional and intratumoral activation. We previously reported on the recruitment of CD11b+ leukocytes due to tumor site-specific enrichment of TNF activity after intravenous administration of a dimeric TNF immunokine with specificity for fibroblast activation protein (FAP). However, TNF-induced chemo-attraction and extravasation of PMNs from blood into the tumor is a multistep process essentially mediated by interleukin 8. With the aim to amplify the TNF-induced and IL-8-mediated chemotactic response, we generated immunocytokines by N-terminal fusion of a human anti-FAP scFv fragment with human IL-8 (IL-872) and its N-terminally truncated form IL-83-72. Due to the dramatic difference in chemotaxis induction in vitro, we favored the mature chemokine fused to the anti-FAP scFv for further investigation in vivo. BALB/c nu/nu mice were simultaneously xenografted with FAP-positive or -negative tumors and extended chemo-attraction of PMNs was only detectable in FAP-expressing tissue after intravenous administration of the anti-FAP scFv-IL-872 construct. As TNF-activated PMNs are likewise producers and primary targets for IL-8, we investigated the therapeutic efficacy of co-administration of both effectors: Sequential application of scFv-IL-872 and dimeric IgG1-TNF fusion proteins significantly enhanced anti-tumor activity when compared either to a single effector treatment regimen or sequential application of non-targeted cytokines, indicating that the tumor-restricted sequential application of IL-872 and TNF is a promising approach for cancer therapy. PMID:19267427

The insulin and IGF1 receptor kinase domains are functional dimers in the activated state

Science.gov (United States)

Cabail, M. Zulema; Li, Shiqing; Lemmon, Eric; Bowen, Mark E.; Hubbard, Stevan R.; Miller, W. Todd

2015-03-01

The insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF1R) are highly related receptor tyrosine kinases with a disulfide-linked homodimeric architecture. Ligand binding to the receptor ectodomain triggers tyrosine autophosphorylation of the cytoplasmic domains, which stimulates catalytic activity and creates recruitment sites for downstream signalling proteins. Whether the two phosphorylated tyrosine kinase domains within the receptor dimer function independently or cooperatively to phosphorylate protein substrates is not known. Here we provide crystallographic, biophysical and biochemical evidence demonstrating that the phosphorylated kinase domains of IR and IGF1R form a specific dimeric arrangement involving an exchange of the juxtamembrane region proximal to the kinase domain. In this dimer, the active position of α-helix C in the kinase N lobe is stabilized, which promotes downstream substrate phosphorylation. These studies afford a novel strategy for the design of small-molecule IR agonists as potential therapeutic agents for type 2 diabetes.

Crystal structure of hyperthermophilic esterase EstE1 and the relationship between its dimerization and thermostability properties

Directory of Open Access Journals (Sweden)

Koh Eunhee

2007-07-01

Full Text Available Abstract Background EstE1 is a hyperthermophilic esterase belonging to the hormone-sensitive lipase family and was originally isolated by functional screening of a metagenomic library constructed from a thermal environmental sample. Dimers and oligomers may have been evolutionally selected in thermophiles because intersubunit interactions can confer thermostability on the proteins. The molecular mechanisms of thermostabilization of this extremely thermostable esterase are not well understood due to the lack of structural information. Results Here we report for the first time the 2.1-Å resolution crystal structure of EstE1. The three-dimensional structure of EstE1 exhibits a classic α/β hydrolase fold with a central parallel-stranded beta sheet surrounded by alpha helices on both sides. The residues Ser154, Asp251, and His281 form the catalytic triad motif commonly found in other α/β hydrolases. EstE1 exists as a dimer that is formed by hydrophobic interactions and salt bridges. Circular dichroism spectroscopy and heat inactivation kinetic analysis of EstE1 mutants, which were generated by structure-based site-directed mutagenesis of amino acid residues participating in EstE1 dimerization, revealed that hydrophobic interactions through Val274 and Phe276 on the β8 strand of each monomer play a major role in the dimerization of EstE1. In contrast, the intermolecular salt bridges contribute less significantly to the dimerization and thermostability of EstE1. Conclusion Our results suggest that intermolecular hydrophobic interactions are essential for the hyperthermostability of EstE1. The molecular mechanism that allows EstE1 to endure high temperature will provide guideline for rational design of a thermostable esterase/lipase using the lipolytic enzymes showing structural similarity to EstE1.

Two Populations Mean-Field Monomer-Dimer Model

Science.gov (United States)

Alberici, Diego; Mingione, Emanuele

2018-04-01

A two populations mean-field monomer-dimer model including both hard-core and attractive interactions between dimers is considered. The pressure density in the thermodynamic limit is proved to satisfy a variational principle. A detailed analysis is made in the limit of one population is much smaller than the other and a ferromagnetic mean-field phase transition is found.

Evaluation of Serum D-dimer Levels in Children with Pneumonia

Directory of Open Access Journals (Sweden)

Nilgün Selçuk Duru

2016-03-01

Full Text Available Aim: The aim of this study was to investigate the relationship of plasma D-dimer levels with duration of hospitalization and radiological and laboratory findings in patients with pneumonia. Methods: Forty-seven patients with pneumonia (31 boys and 16 girls, mean age: 4.2±4.7 years were included in the study. The patients were divided into two groups according to duration of hospitalization and three groups according to radiological findings. D-dimer and other laboratory findings were compared between the groups. Results: The mean serum D-dimer level was 1333.5±1364.4 ng/L. There was no statistically significant difference in D-dimer, leukocyte, erythrocyte sedimentation rate (ESR and C-reactive protein (CRP between the groups divided according to duration of hospitalization. In addition, there was no statistically difference in D-dimer levels between the groups divided according to radiological findings. Age, percentage of neutrophils, ESR and fibrinogen levels were higher in patients with lobar pneumonia when compared with the other groups and CRP level was higher in lobar pneumonia group when compared to interstitial pneumonia group. D-dimer levels were negatively correlated with age and positively correlated with ESR, CRP, and fibrinogen. Conclusion: In our study, D-dimer levels were high in patient with pneumonia. Further studies with a larger number of patients are necessary to determine the role of D-dimer levels as an acutephase reactant in patients with pneumonia

High-Density Renewable Fuels Based on the Selective Dimerization of Pinenes

Science.gov (United States)

2009-01-01

RJ-5, significant ring strain contributing to a high heat of combustion (Table 1). Bulk agricultural waste products, such as cellulose and lignin , are...compact structures and reactive olefin functionalities, these molecules have sig- nificant potential as feedstocks for high-density renewable fuels.2b,7...potential to have heating values exceeding that of JP-10. Given the favorable potential net heat of combustion for these pinene dimers, reactivity

Electron transfer reactions induced by the triplet state of thiacarbocyanine dimers

International Nuclear Information System (INIS)

Chibisov, Alexander K.; Slavnova, Tatyana D.; Goerner, Helmut

2004-01-01

The photoinduced electron transfer between either cationic 5,5 ' -dichloro-3,3 ' ,9-triethylthiacarbocyanine (1) or a structurally similar anionic dye (2) and appropriate donors, e.g. ascorbic acid, and acceptors, e.g. methyl viologen, was studied by ns-laser photolysis. In aqueous solution the dyes in the ground state are present as an equilibrated mixture of dimers and monomers, whereas the triplet state is mainly populated from dimers. The triplet states of both dimers and monomers are quenched by electron donors or acceptors and the rate constant for quenching is generally 2-4 times higher for dimers than for monomers. The kinetics of triplet decay and radical formation and decay as a result of primary and secondary electron transfer were analyzed. While the one-electron reduced dimer decays due to back reactions, the one-electron oxidized dimer rapidly dissociates into the monomer and the monomeric dye radical. For the dimeric dye/donor/acceptor systems the primary photoinduced electron transfer occurs either from the donor or to the acceptor yielding the dimeric dye radicals. The one-electron reduced dimer can be efficiently oxidized by acceptors, e.g. the rate constant for reaction of the dimeric dye radical of 1 with methyl viologen (photoreductive pathway of sensitization) is 1.6x10 9 M -1 s -1 . The photooxidative pathway of sensitization is more complicated; after dissociation of the dimeric dye radical, the monomeric dye radical is reduced in a secondary electron transfer from ascorbic acid, e.g. with a rate constant of 1x10 9 M -1 s -1 for 2, yielding the monomer. On increasing the donor concentration the photooxidative pathway of sensitization is switched to a photoreductive one

Structure of the cold-shock domain protein from Neisseria meningitidis reveals a strand-exchanged dimer

Energy Technology Data Exchange (ETDEWEB)

Ren, Jingshan [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Nettleship, Joanne E.; Sainsbury, Sarah [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Saunders, Nigel J. [Bacterial Pathogenesis and Functional Genomics Group, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Owens, Raymond J., E-mail: ray@strubi.ox.ac.uk [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

2008-04-01

The X-ray crystal structure of the cold-shock domain protein from N. meningitidis reveals a strand-exchanged dimer. The structure of the cold-shock domain protein from Neisseria meningitidis has been solved to 2.6 Å resolution and shown to comprise a dimer formed by the exchange of two β-strands between protein monomers. The overall fold of the monomer closely resembles those of other bacterial cold-shock proteins. The neisserial protein behaved as a monomer in solution and was shown to bind to a hexathymidine oligonucleotide with a stoichiometry of 1:1 and a K{sub d} of 1.25 µM.

Tunneling anisotropic magnetoresistance via molecular π orbitals of Pb dimers

Science.gov (United States)

Schöneberg, Johannes; Ferriani, Paolo; Heinze, Stefan; Weismann, Alexander; Berndt, Richard

2018-01-01

Pb dimers on a ferromagnetic surface are shown to exhibit large tunneling anisotropic magnetoresistance (TAMR) due to molecular π orbitals. Dimers oriented differently with respect to the magnetization directions of a ferromagnetic Fe double layer on W(110) were made with a scanning tunneling microscope. Depending on the dimer orientations, TAMR is absent or as large as 20% at the Fermi level. General arguments and first-principles calculations show that mixing of molecular orbitals due to spin-orbit coupling, which leads to TAMR, is maximal when the magnetization is oriented parallel to the dimer axis.

B{sub c} → B{sub sJ} form factors and B{sub c} decays into B{sub sJ} in covariant light-front approach

Energy Technology Data Exchange (ETDEWEB)

Shi, Yu-Ji; Zhao, Zhen-Xing [Shanghai Jiao-Tong University, INPAC, Shanghai Key Laboratory for Particle Physics and Cosmology, Department of Physics and Astronomy, Shanghai (China); Wang, Wei [Shanghai Jiao-Tong University, INPAC, Shanghai Key Laboratory for Particle Physics and Cosmology, Department of Physics and Astronomy, Shanghai (China); Chinese Academy of Sciences, State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Beijing (China)

2016-10-15

We suggest to study the B{sub s} and its excitations B{sub sJ} in the B{sub c} decays. We calculate the B{sub c} → B{sub sJ} and B{sub c} → B{sub J} form factors within the covariant light-front quark model, where the B{sub sJ} and B{sub J} denote an s-wave or p-wave anti bs and anti bd meson, respectively. The form factors at q{sup 2} = 0 are directly computed while their q{sup 2}-distributions are obtained by extrapolation. The derived form factors are then used to study semileptonic B{sub c} → (B{sub sJ}, B{sub J}) anti lν decays, and nonleptonic B{sub c} → B{sub sJ}π. Branching fractions and polarizations are predicted in the standard model. We find that the branching fractions are sizable and might be accessible at the LHC experiment and future high-energy e{sup +}e{sup -} colliders with a high luminosity at the Z-pole. The future experimental measurements are helpful to study the nonperturbative QCD dynamics in the presence of a heavy spectator and also of great value for the study of spectroscopy. (orig.)

VUV spectroscopy of rare gas van der Waals dimers

International Nuclear Information System (INIS)

Dehmer, P.M.; Pratt, S.T.

1982-01-01

We have undertaken a systematic study of the photoionization spectra of the homonuclear and heteronuclear rare gas dimers in order to better understand the nature of the bonding in the Rydberg states adnd ions of these molecules. We have obtained results for Ar 2 , Kr 2 , Xe 2 , NeAr, NeKr, NeXe, ArKr, ArXe, and KrXe. Of the remaining dimer species (Ne 2 and the Herare gas dimers), only Ne 2 has been studied using photoionization mass spectrometry. The results of the present series of experiments provide information both on the excited states of the neutral dimers and on the ground and excited states of the dimer ions. Using the data obtained in these measurements, we are able to compile for the first time a nearly complete list of ground state dissociation energies for the homonuclear and heteronuclear rare gas dimer ions. Somewhat less complete results are obtained for the excited states of these species. The observed trends in binding energy provide an excellent example of the systematic changes that occur as a result of changes in atomic orbital energies, polarizability, and internuclear distance, and these trends can be explained qualitatively in terms of simple molecular orbital theory

Biochemical and Structural Analysis of Hormone-sensitive Lipase Homolog EstE7: Insight into the Stabilized Dimerization of HSL-Homolog Proteins

International Nuclear Information System (INIS)

Nam, Ki Hyun; Park, Sung Ha; Lee, Won Ho; Hwang, Kwang Yeon

2010-01-01

Hormone sensitive lipase (HSL) plays a major role in energy homeostasis and lipid metabolism. Several crystal structures of HSL-homolog proteins have been identified, which has led to a better understanding of its molecular function. HSLhomolog proteins exit as both monomer and dimer, but the biochemical and structural basis for such oligomeric states has not been successfully elucidated. Therefore, we determined the crystal structure of HSL-homolog protein EstE7 from a metagenome library at 2.2 A resolution and characterized the oligomeric states of EstE7 both structurally and biochemically. EstE7 protein prefers the dimeric state in solution, which is supported by its higher enzymatic activity in the dimeric state. In the crystal form, EstE7 protein shows two-types of dimeric interface. Specifically, dimerization via the external β8-strand occurred through tight association between two pseudosymmetric folds via salt bridges, hydrogen bonds and van der Waals interactions. This dimer formation was similar to that of other HSL-homolog protein structures such as AFEST, BEFA, and EstE1. We anticipate that our results will provide insight into the oligomeric state of HSLhomolog proteins

Four crystal forms of a Bence-Jones protein

International Nuclear Information System (INIS)

Makino, Debora L.; Henschen-Edman, Agnes H.; McPherson, Alexander

2004-01-01

Four crystal forms have been grown and characterized by X-ray diffraction of a Bence-Jones protein collected from the urine of a multiple myeloma patient more than 40 y ago. The trigonal crystal form may shed some light on the formation of fibrils common to certain storage diseases. Four crystal forms have been grown and characterized by X-ray diffraction of a Bence-Jones protein collected from the urine of a multiple myeloma patient more than 40 years ago. Closely related tetragonal and orthorhombic forms belonging to space groups P4 3 2 1 2 and P2 1 2 1 2 1 , with unit-cell parameters a = b = 68.7, c = 182.1 and a = 67.7, b = 69.4, c = 87.3 Å, diffract to 1.5 and 1.9 Å, respectively. Two closely related trigonal forms, both belonging to space group P3 1 21 with unit-cell parameters a = b = 154.3 Å but differing by a doubling of the c axis, one 46.9 Å and the other 94.0 Å, diffract to 2.9 and 2.6 Å resolution, respectively. The trigonal crystal of short c-axis length shows a positive indication of twinning. The trigonal crystal of longer c axis, which appeared only after eight months of incubation at room temperature, is likely to be composed of proteolytically degraded molecules and unlike the other crystal forms contains two entire Bence-Jones dimers in the asymmetric unit. This latter crystal form may shed some light on the formation of fibrils common to certain storage diseases

Reversible dimer formation and stability of the anti-tumour single-chain Fv antibody MFE-23 by neutron scattering, analytical ultracentrifugation, and NMR and FT-IR spectroscopy.

Science.gov (United States)

Lee, Yie Chia; Boehm, Mark K; Chester, Kerry A; Begent, Richard H J; Perkins, Stephen J

2002-06-28

MFE-23 is a single chain Fv (scFv) antibody molecule used to target colorectal cancer through its high affinity for the tumour marker carcinoembryonic antigen (CEA). ScFv molecules are formed from peptide-linked antibody V(H) and V(L) domains, and many of these form dimers. Our recent crystal structure for MFE-23 showed that this formed an unusual symmetric back-to-back association of two monomers that is consistent with a domain-swapped diabody structure. Neutron scattering and modelling fits showed that MFE-23 existed as compact V(H)-V(L)-linked monomers at therapeutically relevant concentrations below 1 mg/ml. Size-exclusion gel chromatography showed that the monomeric and dimeric forms of MFE-23 could be separated, and that the proportions of these two forms depended on the starting MFE-23 concentration. Sedimentation equilibrium experiments by analytical ultracentrifugation at nine concentrations of MFE-23 indicated a reversible monomer-dimer self-association equilibrium with an association constant of 1.9x10(3)-2.2x10(3) M(-1). Sedimentation velocity experiments using the time derivative g(s(*)) method showed that MFE-23-His has a concentration-dependent weight average sedimentation coefficient that increased from 1.8 S for the monomer to about 3-6 S for the dimer. Both values agreed with those calculated from the MFE-23 crystal structure. In relation to the thermal stability of MFE-23, denaturation experiments by (1)H NMR and FT-IR spectroscopy showed that the molecule is stable up to 47 degrees C, after which denaturation was irreversible. MFE-23 dimerisation is discussed in terms of a new model for diabody structures, in which the V(H) and V(L) domains in the monomer are able to dissociate and reassociate to form a dimer, or diabody, but in which symmetric back-to-back contacts between the two monomers are formed. This dimerisation in solution is attributed to the complementary nature of the C-terminal surface of the MFE-23 monomer. Crystal structures for

Extracting dimer structures from simulations of organic-based materials using QM/MM methods

Energy Technology Data Exchange (ETDEWEB)

Pérez-Jiménez, A.J., E-mail: aj.perez@ua.es; Sancho-García, J.C., E-mail: jc.sancho@ua.es

2015-09-28

Highlights: • DFT geometries of isolated dimers in organic crystals differ from experimental ones. • This can be corrected using QM/MM geometry optimizations. • The QM = B3LYP–D3(ZD)/cc-pVDZ and MM = GAFF combination works reasonably well. - Abstract: The functionality of weakly bound organic materials, either in Nanoelectronics or in Materials Science, is known to be strongly affected by their morphology. Theoretical predictions of the underlying structure–property relationships are frequently based on calculations performed on isolated dimers, but the optimized structure of the latter may significantly differ from experimental data even when dispersion-corrected methods are used for it. Here, we address this problem on two organic crystals, namely coronene and 5,6,11,12-tetrachlorotetracene, concluding that it is caused by the absence of the surrounding monomers present in the crystal, and that it can be efficiently cured when the dimer is embedded into a general Quantum Mechanics/Molecular Mechanics (QM/MM) geometry optimization scheme. We also investigate how the size of the MM region affects the results. These findings may be helpful for the simulation of the morphology of active materials in crystalline or glassy samples.

n-Dopants Based on Dimers of Benzimidazoline Radicals: Structures and Mechanism of Redox Reactions.

Science.gov (United States)

Zhang, Siyuan; Naab, Benjamin D; Jucov, Evgheni V; Parkin, Sean; Evans, Eric G B; Millhauser, Glenn L; Timofeeva, Tatiana V; Risko, Chad; Brédas, Jean-Luc; Bao, Zhenan; Barlow, Stephen; Marder, Seth R

2015-07-20

Dimers of 2-substituted N,N'-dimethylbenzimidazoline radicals, (2-Y-DMBI)2 (Y=cyclohexyl (Cyc), ferrocenyl (Fc), ruthenocenyl (Rc)), have recently been reported as n-dopants for organic semiconductors. Here their structural and energetic characteristics are reported, along with the mechanisms by which they react with acceptors, A (PCBM, TIPS-pentacene), in solution. X-ray data and DFT calculations both indicate a longer C-C bond for (2-Cyc-DMBI)2 than (2-Fc-DMBI)2 , yet DFT and ESR data show that the latter dissociates more readily due to stabilization of the radical by Fc. Depending on the energetics of dimer (D2 ) dissociation and of D2 -to-A electron transfer, D2 reacts with A to form D(+) and A(-) by either of two mechanisms, differing in whether the first step is endergonic dissociation or endergonic electron transfer. However, the D(+) /0.5 D2 redox potentials-the effective reducing strengths of the dimers-vary little within the series (ca. -1.9 V vs. FeCp2 (+/0) ) (Cp=cyclopentadienyl) due to cancelation of trends in the D(+/0) potential and D2 dissociation energy. The implications of these findings for use of these dimers as n-dopants, and for future dopant design, are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

n-Dopants Based on Dimers of Benzimidazoline Radicals: Structures and Mechanism of Redox Reactions

KAUST Repository

Zhang, Siyuan

2015-06-18

Dimers of 2-substituted N,N\\'-dimethylbenzimidazoline radicals, (2-Y-DMBI)2 (Y=cyclohexyl (Cyc), ferrocenyl (Fc), ruthenocenyl (Rc)), have recently been reported as n-dopants for organic semiconductors. Here their structural and energetic characteristics are reported, along with the mechanisms by which they react with acceptors, A (PCBM, TIPS-pentacene), in solution. X-ray data and DFT calculations both indicate a longer C-C bond for (2-Cyc-DMBI)2 than (2-Fc-DMBI)2, yet DFT and ESR data show that the latter dissociates more readily due to stabilization of the radical by Fc. Depending on the energetics of dimer (D2) dissociation and of D2-to-A electron transfer, D2 reacts with A to form D+ and A- by either of two mechanisms, differing in whether the first step is endergonic dissociation or endergonic electron transfer. However, the D+/0.5D2 redox potentials-the effective reducing strengths of the dimers-vary little within the series (ca. -1.9V vs. FeCp2+/0) (Cp=cyclopentadienyl) due to cancelation of trends in the D+/0 potential and D2 dissociation energy. The implications of these findings for use of these dimers as n-dopants, and for future dopant design, are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

n-Dopants Based on Dimers of Benzimidazoline Radicals: Structures and Mechanism of Redox Reactions

KAUST Repository

Zhang, Siyuan; Naab, Benjamin D.; Jucov, Evgheni V.; Parkin, Sean; Evans, Eric G B; Millhauser, Glenn L.; Timofeeva, Tatiana V.; Risko, Chad; Bredas, Jean-Luc; Bao, Zhenan; Barlow, Stephen; Marder, Seth R.

2015-01-01

Dimers of 2-substituted N,N'-dimethylbenzimidazoline radicals, (2-Y-DMBI)2 (Y=cyclohexyl (Cyc), ferrocenyl (Fc), ruthenocenyl (Rc)), have recently been reported as n-dopants for organic semiconductors. Here their structural and energetic characteristics are reported, along with the mechanisms by which they react with acceptors, A (PCBM, TIPS-pentacene), in solution. X-ray data and DFT calculations both indicate a longer C-C bond for (2-Cyc-DMBI)2 than (2-Fc-DMBI)2, yet DFT and ESR data show that the latter dissociates more readily due to stabilization of the radical by Fc. Depending on the energetics of dimer (D2) dissociation and of D2-to-A electron transfer, D2 reacts with A to form D+ and A- by either of two mechanisms, differing in whether the first step is endergonic dissociation or endergonic electron transfer. However, the D+/0.5D2 redox potentials-the effective reducing strengths of the dimers-vary little within the series (ca. -1.9V vs. FeCp2+/0) (Cp=cyclopentadienyl) due to cancelation of trends in the D+/0 potential and D2 dissociation energy. The implications of these findings for use of these dimers as n-dopants, and for future dopant design, are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pair Interaction of Catalytical Sphere Dimers in Chemically Active Media

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Jing-Min Shi

2018-01-01

Full Text Available We study the pair dynamics of two self-propelled sphere dimers in the chemically active medium in which a cubic autocatalytic chemical reaction takes place. Concentration gradient around the dimer, created by reactions occurring on the catalytic sphere surface and responsible for the self-propulsion, is greatly influenced by the chemical activities of the environment. Consequently, the pair dynamics of two dimers mediated by the concentration field are affected. In the particle-based mesoscopic simulation, we combine molecular dynamics (MD for potential interactions and reactive multiparticle collision dynamics (RMPC for solvent flow and bulk reactions. Our results indicate three different configurations between a pair of dimers after the collision, i.e., two possible scenarios of bound dimer pairs and one unbound dimer pair. A phase diagram is sketched as a function of the rate coefficients of the environment reactions. Since the pair interactions are the basic elements of larger scale systems, we believe the results may shed light on the understanding of the collective dynamics.

The water dimer II: Theoretical investigations

Energy Technology Data Exchange (ETDEWEB)

Mukhopadhyay, Anamika; Xantheas, Sotiris S.; Saykally, Richard J.

2018-03-29

As the archetype of hydrogen bonding between water molecules, the water dimer has been extensively studied by both theory and experiment for nearly seven decades. In this article, we present a detailed chronological review of the theoretical advances using electronic structure methods pertaining to the structure, hydrogen bonding and vibrational spectroscopy of the water dimer as well as the role of its potential energy surface in the development of classical force fields to describe intermolecular interaction in clusters and liquid water.

Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization

International Nuclear Information System (INIS)

Kim, Sun Young; Song, Kyung-A; Kieff, Elliott; Kang, Myung-Soo

2012-01-01

Highlights: ► Evidence that targeting EBNA1 dimer, an EBV onco-antigen, can be achievable. ► A small molecule and a peptide as EBNA1 dimerization inhibitors identified. ► Both inhibitors associated with EBNA1 and blocked EBNA1 DNA binding activity. ► Also, prevented its dimerization, and repressed viral gene transcription. -- Abstract: Latent Epstein-Barr virus (EBV) infection is associated with human B cell lymphomas and certain carcinomas. EBV episome persistence, replication, and gene expression are dependent on EBV-encoded nuclear antigen 1 (EBNA1)’s DNA binding domain (DBD)/dimerization domain (DD)-mediated sequence-specific DNA binding activity. Homodimerization of EBNA1 is essential for EBNA1 DNA binding and transactivation. In this study, we characterized a novel small molecule EBNA1 inhibitor EiK1, screened from the previous high throughput screening (HTS). The EiK1 compound specifically inhibited the EBNA1-dependent, OriP-enhanced transcription, but not EBNA1-independent transcription. A Surface Plasmon Resonance Biacore assay revealed that EiK1 associates with EBNA1 amino acid 459–607 DBD/DD. Consistent with the SPR data, in vitro gel shift assays showed that EiK1 suppressed the activity of EBNA1 binding to the cognate familial repeats (FR) sequence, but not control RBP-Jκ binding to the Jκ site. Subsequently, a cross-linker-mediated in vitro multimerization assay and EBNA1 homodimerization-dependent yeast two-hybrid assay showed that EiK1 significantly inhibited EBNA1 dimerization. In an attempt to identify more highly specific peptide inhibitors, small peptides encompassing the EBNA1 DBD/DD were screened for inhibition of EBNA1 DBD-mediated DNA binding function. The small peptide P85, covering EBNA1 a.a. 560–574, significantly blocked EBNA1 DNA binding activity in vitro, prevented dimerization in vitro and in vivo, associated with EBNA1 in vitro, and repressed EBNA1-dependent transcription in vivo. Collectively, this study describes two

Small molecule and peptide-mediated inhibition of Epstein-Barr virus nuclear antigen 1 dimerization

Energy Technology Data Exchange (ETDEWEB)

Kim, Sun Young; Song, Kyung-A [Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Samsung Biomedical Research Institute (SBRI), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kieff, Elliott [Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States); Kang, Myung-Soo, E-mail: mkang@skku.edu [Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Samsung Biomedical Research Institute (SBRI), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA 02115 (United States)

2012-07-27

Highlights: Black-Right-Pointing-Pointer Evidence that targeting EBNA1 dimer, an EBV onco-antigen, can be achievable. Black-Right-Pointing-Pointer A small molecule and a peptide as EBNA1 dimerization inhibitors identified. Black-Right-Pointing-Pointer Both inhibitors associated with EBNA1 and blocked EBNA1 DNA binding activity. Black-Right-Pointing-Pointer Also, prevented its dimerization, and repressed viral gene transcription. -- Abstract: Latent Epstein-Barr virus (EBV) infection is associated with human B cell lymphomas and certain carcinomas. EBV episome persistence, replication, and gene expression are dependent on EBV-encoded nuclear antigen 1 (EBNA1)'s DNA binding domain (DBD)/dimerization domain (DD)-mediated sequence-specific DNA binding activity. Homodimerization of EBNA1 is essential for EBNA1 DNA binding and transactivation. In this study, we characterized a novel small molecule EBNA1 inhibitor EiK1, screened from the previous high throughput screening (HTS). The EiK1 compound specifically inhibited the EBNA1-dependent, OriP-enhanced transcription, but not EBNA1-independent transcription. A Surface Plasmon Resonance Biacore assay revealed that EiK1 associates with EBNA1 amino acid 459-607 DBD/DD. Consistent with the SPR data, in vitro gel shift assays showed that EiK1 suppressed the activity of EBNA1 binding to the cognate familial repeats (FR) sequence, but not control RBP-J{kappa} binding to the J{kappa} site. Subsequently, a cross-linker-mediated in vitro multimerization assay and EBNA1 homodimerization-dependent yeast two-hybrid assay showed that EiK1 significantly inhibited EBNA1 dimerization. In an attempt to identify more highly specific peptide inhibitors, small peptides encompassing the EBNA1 DBD/DD were screened for inhibition of EBNA1 DBD-mediated DNA binding function. The small peptide P85, covering EBNA1 a.a. 560-574, significantly blocked EBNA1 DNA binding activity in vitro, prevented dimerization in vitro and in vivo, associated

The specific monomer/dimer equilibrium of the corticotropin-releasing factor receptor type 1 is established in the endoplasmic reticulum.

Science.gov (United States)

Teichmann, Anke; Gibert, Arthur; Lampe, André; Grzesik, Paul; Rutz, Claudia; Furkert, Jens; Schmoranzer, Jan; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

2014-08-29

G protein-coupled receptors (GPCRs) represent the most important drug targets. Although the smallest functional unit of a GPCR is a monomer, it became clear in the past decades that the vast majority of the receptors form dimers. Only very recently, however, data were presented that some receptors may in fact be expressed as a mixture of monomers and dimers and that the interaction of the receptor protomers is dynamic. To date, equilibrium measurements were restricted to the plasma membrane due to experimental limitations. We have addressed the question as to where this equilibrium is established for the corticotropin-releasing factor receptor type 1. By developing a novel approach to analyze single molecule fluorescence cross-correlation spectroscopy data for intracellular membrane compartments, we show that the corticotropin-releasing factor receptor type 1 has a specific monomer/dimer equilibrium that is already established in the endoplasmic reticulum (ER). It remains constant at the plasma membrane even following receptor activation. Moreover, we demonstrate for seven additional GPCRs that they are expressed in specific but substantially different monomer/dimer ratios. Although it is well known that proteins may dimerize in the ER in principle, our data show that the ER is also able to establish the specific monomer/dimer ratios of GPCRs, which sheds new light on the functions of this compartment. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Tah1 helix-swap dimerization prevents mixed Hsp90 co-chaperone complexes

International Nuclear Information System (INIS)

Morgan, Rhodri M. L.; Pal, Mohinder; Roe, S. Mark; Pearl, Laurence H.; Prodromou, Chrisostomos

2015-01-01

A helix swap involving the fifth helix between two adjacently bound Tah1 molecules restores the normal binding environment of the conserved MEEVD peptide of Hsp90. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes with Hsp90 and Tah1. Specific co-chaperone adaptors facilitate the recruitment of client proteins to the Hsp90 system. Tah1 binds the C-terminal conserved MEEVD motif of Hsp90, thus linking an eclectic set of client proteins to the R2TP complex for their assembly and regulation by Hsp90. Rather than the normal complement of seven α-helices seen in other tetratricopeptide repeat (TPR) domains, Tah1 unusually consists of the first five only. Consequently, the methionine of the MEEVD peptide remains exposed to solvent when bound by Tah1. In solution Tah1 appears to be predominantly monomeric, and recent structures have failed to explain how Tah1 appears to prevent the formation of mixed TPR domain-containing complexes such as Cpr6–(Hsp90) 2 –Tah1. To understand this further, the crystal structure of Tah1 in complex with the MEEVD peptide of Hsp90 was determined, which shows a helix swap involving the fifth α-helix between two adjacently bound Tah1 molecules. Dimerization of Tah1 restores the normal binding environment of the bound Hsp90 methionine residue by reconstituting a TPR binding site similar to that in seven-helix-containing TPR domain proteins. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes

Tah1 helix-swap dimerization prevents mixed Hsp90 co-chaperone complexes

Energy Technology Data Exchange (ETDEWEB)

Morgan, Rhodri M. L.; Pal, Mohinder; Roe, S. Mark; Pearl, Laurence H., E-mail: laurence.pearl@sussex.ac.uk; Prodromou, Chrisostomos, E-mail: laurence.pearl@sussex.ac.uk [University of Sussex, Falmer, Brighton BN1 9RQ (United Kingdom)

2015-05-01

A helix swap involving the fifth helix between two adjacently bound Tah1 molecules restores the normal binding environment of the conserved MEEVD peptide of Hsp90. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes with Hsp90 and Tah1. Specific co-chaperone adaptors facilitate the recruitment of client proteins to the Hsp90 system. Tah1 binds the C-terminal conserved MEEVD motif of Hsp90, thus linking an eclectic set of client proteins to the R2TP complex for their assembly and regulation by Hsp90. Rather than the normal complement of seven α-helices seen in other tetratricopeptide repeat (TPR) domains, Tah1 unusually consists of the first five only. Consequently, the methionine of the MEEVD peptide remains exposed to solvent when bound by Tah1. In solution Tah1 appears to be predominantly monomeric, and recent structures have failed to explain how Tah1 appears to prevent the formation of mixed TPR domain-containing complexes such as Cpr6–(Hsp90){sub 2}–Tah1. To understand this further, the crystal structure of Tah1 in complex with the MEEVD peptide of Hsp90 was determined, which shows a helix swap involving the fifth α-helix between two adjacently bound Tah1 molecules. Dimerization of Tah1 restores the normal binding environment of the bound Hsp90 methionine residue by reconstituting a TPR binding site similar to that in seven-helix-containing TPR domain proteins. Dimerization also explains how other monomeric TPR-domain proteins are excluded from forming inappropriate mixed co-chaperone complexes.

Dimerization site 2 of the bacterial DNA-binding protein H-NS is required for gene silencing and stiffened nucleoprotein filament formation.

Science.gov (United States)

Yamanaka, Yuki; Winardhi, Ricksen S; Yamauchi, Erika; Nishiyama, So-Ichiro; Sowa, Yoshiyuki; Yan, Jie; Kawagishi, Ikuro; Ishihama, Akira; Yamamoto, Kaneyoshi

2018-06-15

The bacterial nucleoid-associated protein H-NS is a DNA-binding protein, playing a major role in gene regulation. To regulate transcription, H-NS silences genes, including horizontally acquired foreign genes. Escherichia coli H-NS is 137 residues long and consists of two discrete and independent structural domains: an N-terminal oligomerization domain and a C-terminal DNA-binding domain, joined by a flexible linker. The N-terminal oligomerization domain is composed of two dimerization sites, dimerization sites 1 and 2, which are both required for H-NS oligomerization, but the exact role of dimerization site 2 in gene silencing is unclear. To this end, we constructed a whole set of single amino acid substitution variants spanning residues 2 to 137. Using a well-characterized H-NS target, the slp promoter of the glutamic acid-dependent acid resistance (GAD) cluster promoters, we screened for any variants defective in gene silencing. Focusing on the function of dimerization site 2, we analyzed four variants, I70C/I70A and L75C/L75A, which all could actively bind DNA but are defective in gene silencing. Atomic force microscopy analysis of DNA-H-NS complexes revealed that all of these four variants formed condensed complexes on DNA, whereas WT H-NS formed rigid and extended nucleoprotein filaments, a conformation required for gene silencing. Single-molecule stretching experiments confirmed that the four variants had lost the ability to form stiffened filaments. We conclude that dimerization site 2 of H-NS plays a key role in the formation of rigid H-NS nucleoprotein filament structures required for gene silencing. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

QM/MM studies of cisplatin complexes with DNA dimer and octamer

KAUST Repository

Gkionis, Konstantinos

2012-08-01

Hybrid QM/MM calculations on adducts of cisplatin with DNA dimer and octamer are reported. Starting from the crystal structure of a cisplatin-DNA dimer complex and an NMR structure of a cisplatin-DNA octamer complex, several variants of the ONIOM approach are tested, all employing BHandH for the QM part and AMBER for MM. We demonstrate that a generic set of molecular mechanics parameters for description of Pt-coordination can be used within the subtractive ONIOM scheme without loss of accuracy, such that dedicated parameters for new platinum complexes may not be required. Comparison of optimised structures obtained with different strategies indicates that electrostatic embedding is vital for proper description of the complex, while inclusion of water molecules as explicit solvent further improves performance. The resulting DNA structural parameters are in good general agreement with the experimental structure obtained, particularly when the inherent variability in NMR-derived parameters is taken into account. © 2012 Elsevier B.V.

Inhibition of cyclobutane pyrimidine dimer formation in epidermal p53 gene of UV-irradiated mice by alpha-tocopherol

International Nuclear Information System (INIS)

Chen, W.; Barthelman, M.; Martinez, J.; Alberts, D.; Gensler, H.L.

1997-01-01

Mutations or alterations in the p53 gene have been observed in 50-100% of ultraviolet light (UV)-induced squamous cell carcinoma in humans and animals. Most of the mutations occurred at dipyrimidine sequences, suggesting that pyrimidine dimers in the p53 gene play a role in the pathogenesis of cutaneous squamous cell carcinoma. We previously showed that topical alpha-tocopherol prevents UV-induced skin carcinogenesis in the mouse. In the present study we asked whether topical alpha-tocopherol reduces the level of UV-induced cyclobutane pyrimidine dimers in the murine epidermal p53 gene. Mice received six dorsal applications of 25 mg each of alpha-tocopherol, on alternate days, before exposure to 500 J/m2 of UV-B irradiation. Mice were killed at selected times after irradiation. The level of dimers in the epidermal p53 gene was measured using the T4 endonuclease V assay with quantitative Southern hybridization. Topical alpha-tocopherol caused a 55% reduction in the formation of cyclobutane pyrimidine dimers in the epidermal p53 gene. The rate of reduction of pyrimidine dimers between 1 and 10 hours after irradiation was similar in UV-irradiated mice, regardless of alpha-tocopherol treatment. Therefore, the lower level of cyclobutane pyrimidine dimers in UV-irradiated mice treated with alpha-tocopherol than in control UV-irradiated mice resulted from the prevention of formation of the dimers, and not from enhanced repair of these lesions. Our results indicate that alpha-tocopherol acts as an effective sunscreen in vivo, preventing the formation of premutagenic DNA lesions in a gene known to be important in skin carcinogenesis

The B → D*lv form factor at zero recoil

International Nuclear Information System (INIS)

Simone, J.N.; Hashimoto, S.; El-Khadra, A.X.; Kronfeld, A.S.; Mackenzie, P.B.; Ryan, S.M.

2000-01-01

We describe a model independent lattice QCD method for determining the deviation from unity for h A1 (1), the B → D*lv form factor at zero recoil. We extend the double ratio method previously used to determine the B → Dlv form factor. The bulk of statistical and systematic errors cancel in the double ratios we consider, yielding form factors which promise to reduce present theoretical uncertainties in the determination of parallel V cb parallel. We present results from a prototype calculation at a single lattice spacing corresponding to β = 5.7

Asymmetric monometallic nanorod nanoparticle dimer and related compositions and methods

KAUST Repository

Han, Yu

2016-03-31

The fabrication of asymmetric monometallic nanocrystals with novel properties for plasmonics, nanophotonics and nanoelectronics. Asymmetric monometallic plasmonic nanocrystals are of both fundamental synthetic challenge and practical significance. In an example, a thiol-ligand mediated growth strategy that enables the synthesis of unprecedented Au Nanorod-Au Nanoparticle (AuNR-AuNP) dimers from pre-synthesized AuNR seeds. Using high-resolution electron microscopy and tomography, crystal structure and three-dimensional morphology of the dimer, as well as the growth pathway of the AuNP on the AuNR seed, was investigated for this example. The dimer exhibits an extraordinary broadband optical extinction spectrum spanning the UV, visible, and near infrared regions (300 - 1300 nm). This unexpected property makes the AuNR-AuNP dimer example useful for many nanophotonic applications. In two experiments, the dimer example was tested as a surface- enhanced Raman scattering (SERS) substrate and a solar light harvester for photothermal conversion, in comparison with the mixture of AuNR and AuNP. In the SERS experiment, the dimer example showed an enhancement factor about 10 times higher than that of the mixture, when the excitation wavelength (660 nm) was off the two surface plasmon resonance (SPR) bands of the mixture. In the photothermal conversion experiment under simulated sunlight illumination, the dimer example exhibited an energy conversion efficiency about 1.4 times as high as that of the mixture.

Insights into the photochemical disproportionation of transition metal dimers on the picosecond time scale.

Science.gov (United States)

Lomont, Justin P; Nguyen, Son C; Harris, Charles B

2013-05-09

The reactivity of five transition metal dimers toward photochemical, in-solvent-cage disproportionation has been investigated using picosecond time-resolved infrared spectroscopy. Previous ultrafast studies on [CpW(CO)3]2 established the role of an in-cage disproportionation mechanism involving electron transfer between 17- and 19-electron radicals prior to diffusion out of the solvent cage. New results from time-resolved infrared studies reveal that the identity of the transition metal complex dictates whether the in-cage disproportionation mechanism can take place, as well as the more fundamental issue of whether 19-electron intermediates are able to form on the picosecond time scale. Significantly, the in-cage disproportionation mechanism observed previously for the tungsten dimer does not characterize the reactivity of four out of the five transition metal dimers in this study. The differences in the ability to form 19-electron intermediates are interpreted either in terms of differences in the 17/19-electron equilibrium or of differences in an energetic barrier to associative coordination of a Lewis base, whereas the case for the in-cage vs diffusive disproportionation mechanisms depends on whether the 19-electron reducing agent is genuinely characterized by 19-electron configuration at the metal center or if it is better described as an 18 + δ complex. These results help to better understand the factors that dictate mechanisms of radical disproportionation and carry implications for radical chain mechanisms.

Theoretical investigation of isomerism in dimers (HBO)2, (HBS)2, (HAlO)2 and (HAlS)2

International Nuclear Information System (INIS)

Zyubina, T.S.; Charkin, O.P.

1991-01-01

Using several basic sets and taking into account electron correlation, non-empiric calculations of the structure and relative stability of (HBO) 2 , (HBS) 2 , (HAlO) 2 and (HAlS) 2 dimers were made. Isomers of (HA) 2 Y 2 structure (A = B, Al; Y O,S) have the highest stability, isomers of A 2 (YH) 2 structure are more than 20 kcal/mol less stable. High potential barrier hampers transition frome one isomer to the other. Stability of (HA) 2 Y 2 dimer to decomposition into monomers (HAY+HAY) increases in the series HBS-HBO-HAlS-HAlO

Development of β-linked quaterthiophene and tetrathiafulvalene dimers as new organic semiconductors

International Nuclear Information System (INIS)

Ashizawa, Minoru; Yu, Yan; Niimura, Takuro; Tsuboi, Kazuma; Matsumoto, Hidetoshi; Tanioka, Akihiko; Mori, Takehiko

2010-01-01

A series of β-linked quaterthiophene and tetrathiafulvalene dimers 1-4 has been prepared. Their redox and optical properties are almost the same as the parent monomers indicative of very little interaction between the monomers. Crystal structures of 1, 2, and 4 are highly one-dimensional, in which molecular structure of 1 is planar whereas those of 2 and 4 are in a bent form.

Radiation chemistry of aromatic dimer radical cations

International Nuclear Information System (INIS)

Okamoto, Kazumasa; Tagawa, Seiichi

2009-01-01

π-π Interactions of aromatic molecules are paid attention much in many fields, especially biology, chemistry, and applied physics, represented as protein, DNA, electron donor-accepter complexes, charge transfers, and self assembly molecules. Aromatic molecules including benzene rings are the simplest case to study the π-π interactions. To interpret the charge resonance (CR) structure in the dimer radical cations, spectroscopic and ESR methods have been carried out. The spectroscopic study on the dimer radical ion of molecules with two chromophores would be profitable to identify the electronic and configurational properties. In this article, dynamics of the dimer radical cation of benzenes, polystyrenes, and resist polymers is described on the basis of direct observation of CR band by the nanosecond pulse radiolysis and low temperature γ-radiolysis methods. (author)

Depression of pyrimidine dimer excision from the aspects of U.V. reversibility of irradiated cells

International Nuclear Information System (INIS)

Slamenova, D.; Slezarikova, V.; Masek, F.

1977-01-01

Depression of pyrimidine dimer excision induced in U.V. irradiated E.coli B/r T - trp - Hcr + cells by preirradiation cultivation in conditions of starving for the essential amino acid and thymine does not increase U.V.-reversibility of irradiated cells and does not influence the time of expression of trp + reversions. The expression of mutations becomes completed in control and prestarved cells prior to restoration of postradiation division. Genetic deficiency leads up to their high sensitivity to the mutagenic activity of U.V. irradiation. Expression of trp + revertants in Hcr - type cells does not become completed until after commencement of the postradiation division of irradiated cells. Prestarved E.coli B/r T - trp - Hcr + cells exhibited depression of excision even with postradiation cultivation in the absence of an essential amino acid, which is associated with greater stability of newly synthesized DNA and overall decrease of the death rate of cells. In postradiation starvation for the essential amino acid E.coli B/r T - trp - Hcr - cells irradiated with low U.V. light doses behaved similarly. Control E.coli B/r T - trp - Hcr + cells, cultivated after irradiation without amino acid, excised pyrimidine dimers; they are characterised by high degradation of newly synthesized DNA and increased death rate of cells. (author)

Computational modeling of the bHLH domain of the transcription factor TWIST1 and R118C, S144R and K145E mutants

Directory of Open Access Journals (Sweden)

Maia Amanda M

2012-07-01

Full Text Available Abstract Background Human TWIST1 is a highly conserved member of the regulatory basic helix-loop-helix (bHLH transcription factors. TWIST1 forms homo- or heterodimers with E-box proteins, such as E2A (isoforms E12 and E47, MYOD and HAND2. Haploinsufficiency germ-line mutations of the twist1 gene in humans are the main cause of Saethre-Chotzen syndrome (SCS, which is characterized by limb abnormalities and premature fusion of cranial sutures. Because of the importance of TWIST1 in the regulation of embryonic development and its relationship with SCS, along with the lack of an experimentally solved 3D structure, we performed comparative modeling for the TWIST1 bHLH region arranged into wild-type homodimers and heterodimers with E47. In addition, three mutations that promote DNA binding failure (R118C, S144R and K145E were studied on the TWIST1 monomer. We also explored the behavior of the mutant forms in aqueous solution using molecular dynamics (MD simulations, focusing on the structural changes of the wild-type versus mutant dimers. Results The solvent-accessible surface area of the homodimers was smaller on wild-type dimers, which indicates that the cleft between the monomers remained more open on the mutant homodimers. RMSD and RMSF analyses indicated that mutated dimers presented values that were higher than those for the wild-type dimers. For a more careful investigation, the monomer was subdivided into four regions: basic, helix I, loop and helix II. The basic domain presented a higher flexibility in all of the parameters that were analyzed, and the mutant dimer basic domains presented values that were higher than the wild-type dimers. The essential dynamic analysis also indicated a higher collective motion for the basic domain. Conclusions Our results suggest the mutations studied turned the dimers into more unstable structures with a wider cleft, which may be a reason for the loss of DNA binding capacity observed for in vitro

Magnetic and superconducting competition within the Hubbard dimer. Exact solution

International Nuclear Information System (INIS)

Matlak, M.; Slomska, T.; Grabiec, B.

2005-01-01

We express the Hubbard dimer Hamiltonian H d =Σ 16 α=1 E α vertical stroke E α right angle left angle E α vertical stroke in the second quantization with the use of the Hubbard and spin operators. We consider the case of positive and negative U. We decompose the resulting Hamiltonian into several parts collecting all the terms belonging to the same energy level. Such a decomposition visualizes explicitly all intrinsic interactions competing together and deeply hidden in the original form of the dimer Hamiltonian. Among them are competitive ferromagnetic and antiferromagnetic interactions. There are also hopping terms present which describe Cooper pairs hopping between sites 1 and 2 with positive and negative coupling constants (similar as in Kulik-Pedan, Penson-Kolb models). We show that the competition between intrinsic interactions strongly depends on the model parameters and the averaged occupation number of electrons n element of [0, 4] resulting in different regimes of the model (as e.g. t-J model regime, etc.). (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

12 CFR Appendix B to Part 411 - Disclosure Form To Report Lobbying

Science.gov (United States)

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Disclosure Form To Report Lobbying B Appendix B to Part 411 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES NEW RESTRICTIONS ON LOBBYING Pt. 411, App. B Appendix B to Part 411—Disclosure Form To Report Lobbying EC23SE91.003 EC23SE91.004...

Biocompatible Amphiphilic Hydrogel-Solid Dimer Particles as Colloidal Surfactants.

Science.gov (United States)

Chen, Dong; Amstad, Esther; Zhao, Chun-Xia; Cai, Liheng; Fan, Jing; Chen, Qiushui; Hai, Mingtan; Koehler, Stephan; Zhang, Huidan; Liang, Fuxin; Yang, Zhenzhong; Weitz, David A

2017-12-26

Emulsions of two immiscible liquids can slowly coalesce over time when stabilized by surfactant molecules. Pickering emulsions stabilized by colloidal particles can be much more stable. Here, we fabricate biocompatible amphiphilic dimer particles using a hydrogel, a strongly hydrophilic material, and achieve large contrast in the wetting properties of the two bulbs, resulting in enhanced stabilization of emulsions. We generate monodisperse single emulsions of alginate and shellac solution in oil using a flow-focusing microfluidics device. Shellac precipitates from water and forms a solid bulb at the periphery of the droplet when the emulsion is exposed to acid. Molecular interactions result in amphiphilic dimer particles that consist of two joined bulbs: one hydrogel bulb of alginate in water and the other hydrophobic bulb of shellac. Alginate in the hydrogel compartment can be cross-linked using calcium cations to obtain stable particles. Analogous to surfactant molecules at the interface, the resultant amphiphilic particles stand at the water/oil interface with the hydrogel bulb submerged in water and the hydrophobic bulb in oil and are thus able to stabilize both water-in-oil and oil-in-water emulsions, making these amphiphilic hydrogel-solid particles ideal colloidal surfactants for various applications.

Quantum dissipative dynamics and decoherence of dimers on helium droplets

International Nuclear Information System (INIS)

Schlesinger, Martin

2011-01-01

In this thesis, quantum dynamical simulations are performed in order to describe the vibrational motion of diatomic molecules in a highly quantum environment, so-called helium droplets. We aim to reproduce and explain experimental findings which were obtained from dimers on helium droplets. Nanometer-sized helium droplets contain several thousands of 4 He atoms. They serve as a host for embedded atoms or molecules and provide an ultracold ''refrigerator'' for them. Spectroscopy of molecules in or on these droplets reveals information on both the molecule and the helium environment. The droplets are known to be in the superfluid He II phase. Superfluidity in nanoscale systems is a steadily growing field of research. Spectra obtained from full quantum simulations for the unperturbed dimer show deviations from measurements with dimers on helium droplets. These deviations result from the influence of the helium environment on the dimer dynamics. In this work, a well-established quantum optical master equation is used in order to describe the dimer dynamics effectively. The master equation allows to describe damping fully quantum mechanically. By employing that equation in the quantum dynamical simulation, one can study the role of dissipation and decoherence in dimers on helium droplets. The effective description allows to explain experiments with Rb 2 dimers on helium droplets. Here, we identify vibrational damping and associated decoherence as the main explanation for the experimental results. The relation between decoherence and dissipation in Morse-like systems at zero temperature is studied in more detail. The dissipative model is also used to investigate experiments with K 2 dimers on helium droplets. However, by comparing numerical simulations with experimental data, one finds that further mechanisms are active. Here, a good agreement is obtained through accounting for rapid desorption of dimers. We find that decoherence occurs in the electronic manifold of the

Photon Propagation through Linearly Active Dimers

Directory of Open Access Journals (Sweden)

José Delfino Huerta Morales

2017-06-01

Full Text Available We provide an analytic propagator for non-Hermitian dimers showing linear gain or losses in the quantum regime. In particular, we focus on experimentally feasible realizations of the PT -symmetric dimer and provide their mean photon number and second order two-point correlation. We study the propagation of vacuum, single photon spatially-separable, and two-photon spatially-entangled states. We show that each configuration produces a particular signature that might signal their possible uses as photon switches, semi-classical intensity-tunable sources, or spatially entangled sources to mention a few possible applications.

Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

KAUST Repository

Kim, Jeong Joo

2016-04-09

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

Crystal Structure of PKG I:cGMP Complex Reveals a cGMP-Mediated Dimeric Interface that Facilitates cGMP-Induced Activation

KAUST Repository

Kim, Jeong  Joo; Lorenz, Robin; Arold, Stefan T.; Reger, Albert  S.; Sankaran, Banumathi; Casteel, Darren  E.; Herberg, Friedrich  W.; Kim, Choel

2016-01-01

Cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG) is a key regulator of smooth muscle and vascular tone and represents an important drug target for treating hypertensive diseases and erectile dysfunction. Despite its importance, its activation mechanism is not fully understood. To understand the activation mechanism, we determined a 2.5 Å crystal structure of the PKG I regulatory (R) domain bound with cGMP, which represents the activated state. Although we used a monomeric domain for crystallization, the structure reveals that two R domains form a symmetric dimer where the cGMP bound at high-affinity pockets provide critical dimeric contacts. Small-angle X-ray scattering and mutagenesis support this dimer model, suggesting that the dimer interface modulates kinase activation. Finally, structural comparison with the homologous cyclic AMP-dependent protein kinase reveals that PKG is drastically different from protein kinase A in its active conformation, suggesting a novel activation mechanism for PKG. Kim et al. obtain the first crystal structure of the PKG I R domain bound with cGMP representing its activated state. It reveals a symmetric R dimer where cGMP molecules provide dimeric contacts. This R-R interaction prevents the high-affinity inhibitory interaction between R-C domain and sustains activation. © 2016 Elsevier Ltd.

Depression of pyrimidine dimer excision from the aspects of uv reversibility of irradiated cells

Energy Technology Data Exchange (ETDEWEB)

Slamenova, D; Slezarikova, V; Masek, F [Slovenska Akademia Vied, Bratislava (Czechoslovakia)

1977-04-01

Depression of pyrimidine dimer excision induced in uv-irradiated E.coli B/r T/sup -/trp/sup -/Hcr/sup +/ cells by preirradiation cultivation in conditions of starving for the essential amino acid and thymine does not increase uv-reversibility of irradiated cells and does not influence the time of expression of trp/sup +/ reversions. The expression of mutations becomes completed in control and prestarved cells prior to restoration of postradiation division. Genetic deficiency leads up to their high sensitivity to the mutagenic activity of uv irradiation. Expression of trp/sup +/ revertants in Hcr/sup -/ type cells does not become completed until after commencement of the postradiation division of irradiated cells. Prestarved E.coli B/r T/sup -/trp/sup -/Hcr/sup +/ cells exhibited depression of excision even with postradiation cultivation in the absence of an essential amino acid, which is associated with greater stability of newly synthesized DNA and overall decrease of the death rate of cells. In postradiation starvation for the essential amino acid E.coli B/r T/sup -/trp/sup -/Hcr/sup -/ cells irradiated with low uv light doses behaved similarly. Control E.coli B/r T/sup -/trp/sup -/Hcr/sup +/ cells, cultivated after irradiation without amino acid, excised pyrimidine dimers; they are characterised by high degradation of newly synthesized DNA and increased death rate of cells.

Measurement of the $\\Lambda_{b}^{0}$ Decay Form Factor

CERN Document Server

Abdallah, J; Adam, W; Adzic, P; Albrecht, T; Alderweireld, T; Alemany-Fernandez, R; Allmendinger, T; Allport, P P; Amaldi, Ugo; Amapane, N; Amato, S; Anashkin, E; Andreazza, A; Andringa, S; Anjos, N; Antilogus, P; Apel, W D; Arnoud, Y; Ask, S; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Ballestrero, A; Bambade, P; Barbier, R; Bardin, Dimitri Yuri; Barker, G; Baroncelli, A; Battaglia, Marco; Baubillier, M; Becks, K H; Begalli, M; Behrmann, A; Ben-Haim, E; Benekos, N C; Benvenuti, Alberto C; Bérat, C; Berggren, M; Berntzon, L; Bertrand, D; Besançon, M; Besson, N; Bloch, D; Blom, M; Bluj, M; Bonesini, M; Boonekamp, M; Booth, P S L; Borisov, G; Botner, O; Bouquet, B; Bowcock, T J V; Boyko, I; Bracko, M; Brenner, R; Brodet, E; Brückman, P; Brunet, J M; Bugge, L; Buschmann, P; Calvi, M; Camporesi, T; Canale, V; Carena, F; Castro, N; Cavallo, F R; Chapkin, M M; Charpentier, P; Checchia, P; Chierici, R; Shlyapnikov, P; Chudoba, J; Chung, S U; Cieslik, K; Collins, P; Contri, R; Cosme, G; Cossutti, F; Costa, M J; Crawley, B; Crennell, D J; Cuevas-Maestro, J; D'Hondt, J; Dalmau, J; Da Silva, T; Da Silva, W; Della Ricca, G; De Angelis, A; de Boer, Wim; De Clercq, C; De Lotto, B; De Maria, N; De Min, A; De Paula, L S; Di Ciaccio, Lucia; Di Simone, A; Doroba, K; Drees, J; Dris, M; Eigen, G; Ekelöf, T J C; Ellert, M; Elsing, M; Espirito-Santo, M C; Fanourakis, G K; Fassouliotis, D; Feindt, M; Fernández, J; Ferrer, A; Ferro, F; Flagmeyer, U; Föth, H; Fokitis, E; Fulda-Quenzer, F; Fuster, J A; Gandelman, M; García, C; Gavillet, P; Gazis, E N; Gokieli, R; Golob, B; Gómez-Ceballos, G; Gonçalves, P; Graziani, E; Grosdidier, G; Grzelak, K; Guy, J; Haag, C; Hallgren, A; Hamacher, K; Hamilton, K; Haug, S; Hauler, F; Hedberg, V; Hennecke, M; Herr, H; Hoffman, J; Holmgren, S O; Holt, P J; Houlden, M A; Hultqvist, K; Jackson, J N; Jarlskog, G; Jarry, P; Jeans, D; Johansson, E K; Johansson, P D; Jonsson, P; Joram, C; Jungermann, L; Kapusta, F; Katsanevas, S; Katsoufis, E C; Kernel, G; Kersevan, Borut P; Kerzel, U; Kiiskinen, A P; King, B T; Kjaer, N J; Kluit, P; Kokkinias, P; Kourkoumelis, C; Kuznetsov, O; Krumshtein, Z; Kucharczyk, M; Lamsa, J; Leder, G; Ledroit, F; Leinonen, L; Leitner, R; Lemonne, J; Lepeltier, V; Lesiak, T; Liebig, W; Liko, D; Lipniacka, A; Lopes, J H; López, J M; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J; Malek, A; Maltezos, S; Mandl, F; Marco, J; Marco, R; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Martínez-Rivero, C; Masik, J; Mastroyiannopoulos, N; Matorras, F; Matteuzzi, C; Mazzucato, F; Mazzucato, M; McNulty, R; Meroni, C; Meyer, W T; Myagkov, A; Migliore, E; Mitaroff, W A; Mjörnmark, U; Moa, T; Moch, M; Mönig, K; Monge, R; Montenegro, J; Moraes, D; Moreno, S; Morettini, P; Müller, U; Münich, K; Mulders, M; Mundim, L M; Murray, W; Muryn, B; Myatt, Gerald; Myklebust, T; Nassiakou, M; Navarria, Francesco Luigi; Nawrocki, K; Nicolaidou, R; Nikolenko, M; Oblakowska-Mucha, A; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Österberg, K; Ouraou, A; Oyanguren, A; Paganoni, M; Paiano, S; Palacios, J P; Palka, H; Papadopoulou, T D; Pape, L; Parkes, C; Parodi, F; Parzefall, U; Passeri, A; Passon, O; Peralta, L; Perepelitsa, V F; Perrotta, A; Petrolini, A; Piedra, J; Pieri, L; Pierre, F; Pimenta, M; Piotto, E; Podobnik, T; Poireau, V; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Pukhaeva, N; Pullia, Antonio; Rames, J; Ramler, L; Read, A; Rebecchi, P; Rehn, J; Reid, D; Reinhardt, R; Renton, P B; Richard, F; Rídky, J; Rivero, M; Rodríguez, D; Romero, A; Ronchese, P; Rosenberg, E I; Roudeau, Patrick; Rovelli, T; Ruhlmann-Kleider, V; Ryabtchikov, D; Sadovskii, A; Salmi, L; Salt, J; Savoy-Navarro, A; Schwickerath, U; Segar, A; Sekulin, R L; Siebel, M; Sissakian, A N; Smadja, G; Smirnova, O G; Sokolov, A; Sopczak, A; Sosnowski, R; Spassoff, Tz; Stanitzki, M; Stocchi, A; Strauss, J; Stugu, B; Szczekowski, M; Szeptycka, M; Szumlak, T; Tabarelli de Fatis, T; Taffard, A C; Tegenfeldt, F; Timmermans, J; Tkatchev, L G; Tobin, M; Todorovova, S; Tomé, B; Tonazzo, A; Tortosa, P; Travnicek, P; Treille, D; Tristram, G; Trochimczuk, M; Troncon, C; Turluer, M L; Tyapkin, I A; Tyapkin, P; Tzamarias, S; Uvarov, V; Valenti, G; van Dam, P; Van Eldik, J; Van Lysebetten, A; Van Remortel, N; Van Vulpen, I B; Vegni, G; Veloso, F; Venus, W A; Verdier, P; Verzi, V; Vilanova, D; Vitale, L; Vrba, V; Wahlen, H; Washbrook, A J; Weiser, C; Wicke, D; Wickens, J H; Wilkinson, G; Winter, M; Witek, M; Yushchenko, O P; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zhuravlov, V; Zimin, N I; Zinchenko, A I; Zupan, M

2004-01-01

The form factor of Lambda_b^0 baryons is estimated using 3.46 10^6 hadronic Z decays collected by the DELPHI experiment between 1992 and 1995. Charmed Lambda_c^+ baryons fully reconstructed in the pK-pi+, pK0_S, and Lambda pi+pi+pi- modes, are associated to a lepton with opposite charge in order to select Lambda_b^0 -> Lambda_c^+ l^- anti-nu_l decays. From a combined likelihood and event rate fit to the distribution of the Isgur-Wise variable w, and using the Heavy Quark Effective Theory (HQET), the slope of the b-baryon form factor is measured to be: rho-hat^2 = 2.03 +/- 0.46 (stat) ^{+0.72}_{-1.00} (syst). The exclusive semileptonic branching fraction Br(Lambda_b^0 -> Lambda_c^+ l^- anti-nu_l) can be derived from rho-hat^2 and is found to be (5.0^{+1.1}_{-0.8} (stat) ^{+1.6}_{-1.2} (syst))%. Limits on other branching fractions are also obtained.

12 CFR Appendix B to Part 707 - Model Clauses and Sample Forms

Science.gov (United States)

2010-01-01

...) B-8—Sample Form (Money Market Share Account Disclosures) B-9—Sample Form (Term Share (Certificate... money market accounts. These are some of the more common limitations applicable. The credit union... will assist members in reviewing and understanding the change. B-3Model Clauses for Pre-Maturity...

Fiber optic D dimer biosensor

Science.gov (United States)

Glass, Robert S.; Grant, Sheila A.

1999-01-01

A fiber optic sensor for D dimer (a fibrinolytic product) can be used in vivo (e.g., in catheter-based procedures) for the diagnosis and treatment of stroke-related conditions in humans. Stroke is the third leading cause of death in the United States. It has been estimated that strokes and stroke-related disorders cost Americans between $15-30 billion annually. Relatively recently, new medical procedures have been developed for the treatment of stroke. These endovascular procedures rely upon the use of microcatheters. These procedures could be facilitated with this sensor for D dimer integrated with a microcatheter for the diagnosis of clot type, and as an indicator of the effectiveness, or end-point of thrombolytic therapy.

Singlet fission in pentacene dimers

Science.gov (United States)

Zirzlmeier, Johannes; Lehnherr, Dan; Coto, Pedro B.; Chernick, Erin T.; Casillas, Rubén; Basel, Bettina S.; Thoss, Michael; Tykwinski, Rik R.; Guldi, Dirk M.

2015-01-01

Singlet fission (SF) has the potential to supersede the traditional solar energy conversion scheme by means of boosting the photon-to-current conversion efficiencies beyond the 30% Shockley–Queisser limit. Here, we show unambiguous and compelling evidence for unprecedented intramolecular SF within regioisomeric pentacene dimers in room-temperature solutions, with observed triplet quantum yields reaching as high as 156 ± 5%. Whereas previous studies have shown that the collision of a photoexcited chromophore with a ground-state chromophore can give rise to SF, here we demonstrate that the proximity and sufficient coupling through bond or space in pentacene dimers is enough to induce intramolecular SF where two triplets are generated on one molecule. PMID:25858954

Optical properties of electrically connected plasmonic nanoantenna dimer arrays

Science.gov (United States)

Zimmerman, Darin T.; Borst, Benjamin D.; Carrick, Cassandra J.; Lent, Joseph M.; Wambold, Raymond A.; Weisel, Gary J.; Willis, Brian G.

2018-02-01

We fabricate electrically connected gold nanoantenna arrays of homodimers and heterodimers on silica substrates and present a systematic study of their optical properties. Electrically connected arrays of plasmonic nanoantennas make possible the realization of novel photonic devices, including optical sensors and rectifiers. Although the plasmonic response of unconnected arrays has been studied extensively, the present study shows that the inclusion of nanowire connections modifies the device response significantly. After presenting experimental measurements of optical extinction for unconnected dimer arrays, we compare these to measurements of dimers that are interconnected by gold nanowire "busbars." The connected devices show the familiar dipole response associated with the unconnected dimers but also show a second localized surface plasmon resonance (LSPR) that we refer to as the "coupled-busbar mode." Our experimental study also demonstrates that the placement of the nanowire along the antenna modifies the LSPR. Using finite-difference time-domain simulations, we confirm the experimental results and investigate the variation of dimer gap and spacing. Changing the dimer gap in connected devices has a significantly smaller effect on the dipole response than it does in unconnected devices. On the other hand, both LSPR modes respond strongly to changing the spacing between devices in the direction along the interconnecting wires. We also give results for the variation of E-field strength in the dimer gap, which will be important for any working sensor or rectenna device.

Metal membrane with dimer slots as a universal polarizer

Science.gov (United States)

Zhukovsky, Sergej; Zalkovskij, Maksim; Malureanu, Radu; Kremers, Christian; Chigrin, Dmitry; Tang, Peter T.; Jepsen, Peter U.; Lavrinenko, Andrei V.

2014-03-01

In this work, we show theoretically and confirm experimentally that thin metal membranes patterned with an array of slot dimers (or their Babinet analogue with metal rods) can function as a versatile spectral and polarization filter. We present a detailed covariant multipole theory for the electromagnetic response of an arbitrary dimer based on the Green functions approach. The theory confirms that a great variety of polarization properties, such as birefringence, chirality and elliptical dichroism, can be achieved in a metal layer with such slot-dimer patterning (i.e. in a metasurface). Optical properties of the metasurface can be extensively tuned by varying the geometry (shape and dimensions) of the dimer, for example, by adjusting the sizes and mutual placement of the slots (e.g. inter-slot distance and alignment angle). Three basic shapes of dimers are analyzed: II-shaped (parallel slots), V-shaped, and T-shaped. These particular shapes of dimers are found to be sensitive to variations of the slots lengths and orientation of elements. Theoretical results are well supported by full-wave three-dimensional simulations. Our findings were verified experimentally on the metal membranes fabricated using UV lithography with subsequent Ni growth. Such metasurfaces were characterized using time-domain THz spectroscopy. The samples exhibit pronounced optical activity (500 degrees per wavelength) and high transmission: even though the slots cover only 4.3 % of the total membrane area the amplitude transmission reaches 0.67 at the resonance frequency 0.56 THz.

Comparative action spectra for pyrimidine dimer formation in Cloudman S91 mouse melanoma and EMT6 mouse mammary carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Hill, H Z [New Jersey, Medical School, Newark (USA); Setlow, R B [Brookhaven National Lab., Upton, NY (USA)

1982-05-01

Pyrimidine dimer formation in melanotic mouse melanoma cells, Cloudman S91H-, and in mouse mammary carcinoma cells, EMT6, was compared as a function of wavelength by irradiating equal numbers of cells from the two cell lines simultaneously. More dimers were formed in EMT6 than in S91H- by light of wavelengths less than 289nm, while light of higher wavelengths caused equivalent dimer formation, as measured by the Micrococcus luteus UV-endonuclease assay. The cells of S91H- are lightly melanotic, yet shielding at lower wavelengths is considerable. It is speculated that melanin pigmentation arose by selection during an evolutionary period when UV-C light reaching the earth's surface was significantly greater than it is today.

Neurodevelopmental Expression Profile of Dimeric and Monomeric Group 1 mGluRs: Relevance to Schizophrenia Pathogenesis and Treatment.

Science.gov (United States)

Lum, Jeremy S; Fernandez, Francesca; Matosin, Natalie; Andrews, Jessica L; Huang, Xu-Feng; Ooi, Lezanne; Newell, Kelly A

2016-10-10

Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia. Under control conditions, mGluR1α dimer expression increased between juvenile and adolescence (209-328%), while monomeric levels remained consistent. Dimeric mGluR5 was steadily expressed across all time points; monomeric mGluR5 was present in juveniles, dramatically declining at adolescence and adulthood (-97-99%). The mGluR regulators, Homer 1b/c and Norbin, significantly increased with age in the PFC and hippocampus. Perinatal PCP treatment significantly increased juvenile dimeric mGluR5 levels in the PFC and hippocampus (37-50%) but decreased hippocampal mGluR1α (-50-56%). Perinatal PCP treatment also reduced mGluR1α dimer levels in the PFC at adulthood (-31%). These results suggest that Group 1 mGluRs have distinct dimeric and monomeric neurodevelopmental patterns, which may impact their pharmacological profiles at specific ages. Perinatal PCP treatment disrupted the early expression of Group 1 mGluRs which may underlie neurodevelopmental alterations observed in this model.

Four crystal forms of a Bence-Jones protein

Energy Technology Data Exchange (ETDEWEB)

Makino, Debora L.; Henschen-Edman, Agnes H.; McPherson, Alexander, E-mail: amcphers@uci.edu [Molecular Biology and Biochemistry, University of California, Irvine, 560 Steinhaus Hall, Irvine, CA 92697-3900 (United States)

2005-01-01

Four crystal forms have been grown and characterized by X-ray diffraction of a Bence-Jones protein collected from the urine of a multiple myeloma patient more than 40 y ago. The trigonal crystal form may shed some light on the formation of fibrils common to certain storage diseases. Four crystal forms have been grown and characterized by X-ray diffraction of a Bence-Jones protein collected from the urine of a multiple myeloma patient more than 40 years ago. Closely related tetragonal and orthorhombic forms belonging to space groups P4{sub 3}2{sub 1}2 and P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = b = 68.7, c = 182.1 and a = 67.7, b = 69.4, c = 87.3 Å, diffract to 1.5 and 1.9 Å, respectively. Two closely related trigonal forms, both belonging to space group P3{sub 1}21 with unit-cell parameters a = b = 154.3 Å but differing by a doubling of the c axis, one 46.9 Å and the other 94.0 Å, diffract to 2.9 and 2.6 Å resolution, respectively. The trigonal crystal of short c-axis length shows a positive indication of twinning. The trigonal crystal of longer c axis, which appeared only after eight months of incubation at room temperature, is likely to be composed of proteolytically degraded molecules and unlike the other crystal forms contains two entire Bence-Jones dimers in the asymmetric unit. This latter crystal form may shed some light on the formation of fibrils common to certain storage diseases.

A Model for Dimerization of the SOX Group E Transcription Factor Family.

Directory of Open Access Journals (Sweden)

Sarah N Ramsook

Full Text Available Group E members of the SOX transcription factor family include SOX8, SOX9, and SOX10. Preceding the high mobility group (HMG domain in each of these proteins is a thirty-eight amino acid region that supports the formation of dimers on promoters containing tandemly inverted sites. The purpose of this study was to obtain new structural insights into how the dimerization region functions with the HMG domain. From a mutagenic scan of the dimerization region, the most essential amino acids of the dimerization region were clustered on the hydrophobic face of a single, predicted amphipathic helix. Consistent with our hypothesis that the dimerization region directly contacts the HMG domain, a peptide corresponding to the dimerization region bound a preassembled HMG-DNA complex. Sequence conservation among Group E members served as a basis to identify two surface exposed amino acids in the HMG domain of SOX9 that were necessary for dimerization. These data were combined to make a molecular model that places the dimerization region of one SOX9 protein onto the HMG domain of another SOX9 protein situated at the opposing site of a tandem promoter. The model provides a detailed foundation for assessing the impact of mutations on SOX Group E transcription factors.

Excitonic Behavior of Rhodamine Dimers: A Single-Molecule Study

NARCIS (Netherlands)

Hernando Campos, J.; van der Schaaf, Martijn; van Dijk, E.M.H.P.; Sauer, Markus; Garcia Parajo, M.F.; van Hulst, N.F.

2003-01-01

The optical behavior of a dimer of tetramethylrhodamine-5-isothiocyanate has been investigated by means of single-molecule measurements. Bulk absorption and fluorescence spectra show the existence of two populations of the dimer molecule that exhibit distinct excitonic interactions (strong and weak

DENV gene of bacteriophage T4 codes for both pyrimidine dimer-DNA glycosylase and apyrimidinic endonuclease activities

International Nuclear Information System (INIS)

McMillan, S.; Edenberg, H.J.; Radany, E.H.; Friedberg, R.C.; Friedberg, E.C.

1981-01-01

Recent studies have shown that purified preparations of phage T4 UV DNA-incising activity (T4 UV endonuclease or endonuclease V of phase T4) contain a pyrimidine dimer-DNA glycosylase activity that catalyzes hydrolysis of the 5' glycosyl bond of dimerized pyrimidines in UV-irradiated DNA. Such enzyme preparations have also been shown to catalyze the hydrolysis of phosphodiester bonds in UV-irradiated DNA at a neutral pH, presumably reflecting the action of an apurinic/apyrimidinic endonuclease at the apyrimidinic sites created by the pyrimidine dimer-DNA glycosylase. In this study we found that preparations of T4 UV DNA-incising activity contained apurinic/apyrimidinic endonuclease activity that nicked depurinated form I simian virus 40 DNA. Apurinic/apyrimidinic endonuclease activity was also found in extracts of Escherichia coli infected with T4 denV + phage. Extracts of cells infected with T4 denV mutants contained significantly lower levels of apurinic/apyrimidinic endonuclease activity; these levels were no greater than the levels present in extracts of uninfected cells. Furthermore, the addition of DNA containing UV-irradiated DNA and T4 enzyme resulted in competition for pyrimidine dimer-DNA glycosylase activity against the UV-irradiated DNA. On the basis of these results, we concluded that apurinic/apyrimidinic endonuclease activity is encoded by the denV gene of phage T4, the same gene that codes for pyrimidine dimer-DNA glycosylase activity

Determination of four forms of vitamin B12 and other B vitamins in seawater by liquid chromatography/tandem mass spectrometry.

Science.gov (United States)

Heal, Katherine R; Carlson, Laura Truxal; Devol, Allan H; Armbrust, E Virginia; Moffett, James W; Stahl, David A; Ingalls, Anitra E

2014-11-30

Vitamin B(12) is an essential nutrient for more than half of surveyed marine algae species, but methods for directly measuring this important cofactor in seawater are limited. Current mass spectrometry methods do not quantify all forms of B(12), potentially missing a significant portion of the B(12) pool. We present a method to measure vitamins B(1), B(2), B(6), B(7) and four forms of B(12) dissolved in seawater. The method entails solid-phase extraction, separation by ultra-performance liquid chromatography, and detection by triple-quadrupole tandem mass spectrometry using stable-isotope-labeled internal standards. We demonstrated the use of this method in the environment by analyzing B(12) concentrations at different depths in the Hood Canal, part of the Puget Sound estuarine system in Washington State. Recovery of vitamin B(12) forms during the preconcentration steps was >71% and the limits of detection were B(12) in seawater at our field site. We developed a method for quantifying four forms of B(12) in seawater by liquid chromatography/mass spectrometry with the option of simultaneous analysis of vitamins B(1), B(2), B(6), and B(7). We validated the method and demonstrated its application in the field. Copyright © 2014 John Wiley & Sons, Ltd.

Solution NMR investigation of the response of the lactose repressor core domain dimer to hydrostatic pressure.

Science.gov (United States)

Fuglestad, Brian; Stetz, Matthew A; Belnavis, Zachary; Wand, A Joshua

2017-12-01

Previous investigations of the sensitivity of the lac repressor to high-hydrostatic pressure have led to varying conclusions. Here high-pressure solution NMR spectroscopy is used to provide an atomic level view of the pressure induced structural transition of the lactose repressor regulatory domain (LacI* RD) bound to the ligand IPTG. As the pressure is raised from ambient to 3kbar the native state of the protein is converted to a partially unfolded form. Estimates of rotational correlation times using transverse optimized relaxation indicates that a monomeric state is never reached and that the predominate form of the LacI* RD is dimeric throughout this pressure change. Spectral analysis suggests that the pressure-induced transition is localized and is associated with a volume change of approximately -115mlmol -1 and an average pressure dependent change in compressibility of approximately 30mlmol -1 kbar -1 . In addition, a subset of resonances emerge at high-pressures indicating the presence of a non-native but folded alternate state. Copyright © 2017 Elsevier B.V. All rights reserved.

Stability improvement of the Nieuwland catalyst in the dimerization of acetylene to monovinylacetylene

Institute of Scientific and Technical Information of China (English)

Jianguo Liu; Yizan Zuo; Minghan Han; Zhanwen Wang; Dezheng Wang

2012-01-01

In the process of dimerization of acetylene to produce monovinylacetylene (MVA),the loss of active component CuCl in the Nieuwland catalyst due to the formation of a dark red precipitate was investigated.The formula of the precipitate was CuCl·2C2H2·1/5NH3,and it was presumed to be formed by the combination of NH3,C2H2 and [Cu]-acetylene π-complex,which was an intermediate in the dimerization reaction.The addition of hydrochloric acid into the catalyst can reduce the formation of precipitate,whereas excessive H+ is unfavorable to the dimerization reaction of acetylene.To balance between high acetylene conversion and low loss rate of CuCl,the optimum mass percentage of HCl in the added hydrochloric acid was determined.The result showed the optimum mass percentage of HCl decreased from 5.0％ to 3.2％ when the space velocity of acetylene was from 140 h-1 to 360 h-1.The result in this work also indicated the pH of the Nieuwland catalyst should be kept in the range of 5.80-5.97 during the reaction process,which was good for both catalyst life and acetylene conversion.

Photoionization of helium dimers; Photoionisation von Heliumdimeren

Energy Technology Data Exchange (ETDEWEB)

Havermeier, Tilo

2010-06-09

The helium dimer is one of the most weakly bound systems in the universe. This makes it an interesting quantum mechanical object for investigation. These Van der Waals Clusters can be produced in an expansion of a cryogenic gas jet through a small nozzle into vacuum. In the present experiment we examine the interaction of He dimers with synchrotron radiation at an energy range from 64 to 78 eV. We observed different pathways leading to single ionization of both He atoms of the dimer compound. This two close standing ions begin now to dissociate in cause of their coulomb potential. All charged fragments were detected in coincidence with a COLTRIMS system. Especially Interatomic Coulombic Decay (ICD) and the two step process (TS1) were clearly identified. Furthermore a distribution of the internuclear distance was obtained from the measured Kinetic Energy Release (KER). (orig.)

Water dimers in the atmosphere III: equilibrium constant from a flexible potential.

Science.gov (United States)

Scribano, Yohann; Goldman, Nir; Saykally, R J; Leforestier, Claude

2006-04-27

We present new results for the water dimer equilibrium constant K(p)(T) in the range 190-390 K, using a flexible potential energy surface fitted to spectroscopical data. The increased numerical complexity due to explicit consideration of the monomer vibrations is handled via an adiabatic (6 + 6)d decoupling between intra- and intermolecular modes. The convergence of the canonical partition function of the dimer is ensured by computing all energy levels up to dissociation for total angular momentum values J = 0-5 and using an extrapolation scheme to higher values. The newly calculated values for K(p)(T) are in very good agreement with available experimental data at room temperature. At higher temperatures, an analysis of the convergence of the partition function reveals that quasi-bound states are likely to contribute to the equilibrium constant. Additional thermodynamical quantities (deltaG, deltaH, deltaS, and C(p)) have also been determined and fit to quadratic expressions a + bT + cT2.

Exact Solution of a Generalized Nonlinear Schrodinger Equation Dimer

DEFF Research Database (Denmark)

Christiansen, Peter Leth; Maniadis, P.; Tsironis, G.P.

1998-01-01

We present exact solutions for a nonlinear dimer system defined throught a discrete nonlinear Schrodinger equation that contains also an integrable Ablowitz-Ladik term. The solutions are obtained throught a transformation that maps the dimer into a double Sine-Gordon like ordinary nonlinear...... differential equation....

Formation of thymine containing dimers in skin exposed to ultraviolet radiation

Energy Technology Data Exchange (ETDEWEB)

Johnson, B E [Dundee Univ. (UK)

1978-01-01

Nuclear DNA appears to be the major molecular target for the inhibitory, mutagenic and lethal effects of ultraviolet radiation on cells in culture. Cyclobutyl dimers between adjacent pyrimidine bases, the major photochemical lesions for these effects in prokaryotes, also play a part in UVR effects on eukaryotes cells. Pyrimidine dimers have been isolated from in vivo UV-irradiated guinea pig and mouse skin. The wavelength dependence for dimer induction is similar to that for acute skin reactions but no direct causal relationship has been established. Sunlight UVR may induce dimers in skin DNA. Excision of dimers from mouse skin in vivo is deficient as it is for most rodent cells in culture; human cell excision is efficient and the difficulties in interpretation of UV-carcinogenesis results with mice in terms of human skin cancer are therefore increased.

B S Sekhon

Indian Academy of Sciences (India)

Gemini (dimeric) Surfactants - The Two-Faced Molecules · B S Sekhon · More Details Fulltext PDF. Volume 9 Issue 8 August 2004 pp 35-45 General Article. Detergents – Zeolites and Enzymes Excel Cleaning Power · B S Sekhon Manjeet K Sangha · More Details Fulltext PDF. Volume 11 Issue 4 April 2006 pp 75-90 General ...

Artificial light harvesting by dimerized Möbius ring

Science.gov (United States)

Xu, Lei; Gong, Z. R.; Tao, Ming-Jie; Ai, Qing

2018-04-01

We theoretically study artificial light harvesting by a Möbius ring. When the donors in the ring are dimerized, the energies of the donor ring are split into two subbands. Because of the nontrivial Möbius boundary condition, both the photon and acceptor are coupled to all collective-excitation modes in the donor ring. Therefore, the quantum dynamics in the light harvesting is subtly influenced by dimerization in the Möbius ring. It is discovered that energy transfer is more efficient in a dimerized ring than that in an equally spaced ring. This discovery is also confirmed by a calculation with the perturbation theory, which is equivalent to the Wigner-Weisskopf approximation. Our findings may be beneficial to the optimal design of artificial light harvesting.

Structural basis of genomic RNA (gRNA) dimerization and packaging determinants of mouse mammary tumor virus (MMTV).

Science.gov (United States)

Aktar, Suriya J; Vivet-Boudou, Valérie; Ali, Lizna M; Jabeen, Ayesha; Kalloush, Rawan M; Richer, Delphine; Mustafa, Farah; Marquet, Roland; Rizvi, Tahir A

2014-11-14

One of the hallmarks of retroviral life cycle is the efficient and specific packaging of two copies of retroviral gRNA in the form of a non-covalent RNA dimer by the assembling virions. It is becoming increasingly clear that the process of dimerization is closely linked with gRNA packaging, and in some retroviruses, the latter depends on the former. Earlier mutational analysis of the 5' end of the MMTV genome indicated that MMTV gRNA packaging determinants comprise sequences both within the 5' untranslated region (5' UTR) and the beginning of gag. The RNA secondary structure of MMTV gRNA packaging sequences was elucidated employing selective 2'hydroxyl acylation analyzed by primer extension (SHAPE). SHAPE analyses revealed the presence of a U5/Gag long-range interaction (U5/Gag LRI), not predicted by minimum free-energy structure predictions that potentially stabilizes the global structure of this region. Structure conservation along with base-pair covariations between different strains of MMTV further supported the SHAPE-validated model. The 5' region of the MMTV gRNA contains multiple palindromic (pal) sequences that could initiate intermolecular interaction during RNA dimerization. In vitro RNA dimerization, SHAPE analysis, and structure prediction approaches on a series of pal mutants revealed that MMTV RNA utilizes a palindromic point of contact to initiate intermolecular interactions between two gRNAs, leading to dimerization. This contact point resides within pal II (5' CGGCCG 3') at the 5' UTR and contains a canonical "GC" dyad and therefore likely constitutes the MMTV RNA dimerization initiation site (DIS). Further analyses of these pal mutants employing in vivo genetic approaches indicate that pal II, as well as pal sequences located in the primer binding site (PBS) are both required for efficient MMTV gRNA packaging. Employing structural prediction, biochemical, and genetic approaches, we show that pal II functions as a primary point of contact between

Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.

Directory of Open Access Journals (Sweden)

Masao Terasawa

Full Text Available The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain the Dbl homology domain typically found in guanine nucleotide exchange factors (GEFs, DOCK2 mediates the GTP-GDP exchange reaction for Rac via its DOCK homology region (DHR-2 (also known as CZH2 or Docker domain. DOCK2 DHR-2 domain is composed of three lobes, and Rac binding site and catalytic center are generated entirely from lobes B and C. On the other hand, lobe A has been implicated in dimer formation, yet its physiological significance remains unknown. Here, we report that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration. We found that unlike wild-type DOCK2, DOCK2 mutant lacking lobe A failed to restore motility and polarity when expressed in thymoma cells and primary T cells lacking endogenous expression of DOCK2. Similar results were obtained with the DOCK2 point mutant having a defect in dimerization. Deletion of lobe A from the DHR-2 domain did not affect Rac GEF activity in vitro. However, fluorescence resonance energy transfer analyses revealed that lobe A is required for DOCK2 to activate Rac effectively during cell migration. Our results thus indicate that DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and Rac are localized to the plasma membrane.

Dimerization of the voltage-sensing phosphatase controls its voltage-sensing and catalytic activity.

Science.gov (United States)

Rayaprolu, Vamseedhar; Royal, Perrine; Stengel, Karen; Sandoz, Guillaume; Kohout, Susy C

2018-05-07

Multimerization is a key characteristic of most voltage-sensing proteins. The main exception was thought to be the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP). In this study, we show that multimerization is also critical for Ci-VSP function. Using coimmunoprecipitation and single-molecule pull-down, we find that Ci-VSP stoichiometry is flexible. It exists as both monomers and dimers, with dimers favored at higher concentrations. We show strong dimerization via the voltage-sensing domain (VSD) and weak dimerization via the phosphatase domain. Using voltage-clamp fluorometry, we also find that VSDs cooperate to lower the voltage dependence of activation, thus favoring the activation of Ci-VSP. Finally, using activity assays, we find that dimerization alters Ci-VSP substrate specificity such that only dimeric Ci-VSP is able to dephosphorylate the 3-phosphate from PI(3,4,5)P 3 or PI(3,4)P 2 Our results indicate that dimerization plays a significant role in Ci-VSP function. © 2018 Rayaprolu et al.

DFT study of small fullerene dimer complexes C_2_0-N_m@C_n (m = 1-6 and n = 24, 28, 32, 36 and 40)

International Nuclear Information System (INIS)

Kaur, Sandeep; Sharma, Amrish; Mudahar, Isha

2016-01-01

First principle calculations based on density functional theory were performed to calculate the structural and electronic properties of C_2_0-N_m@C_n dimer complexes. The calculated binding energies of the complexes formed are comparable to C_6_0 dimer which ensures their stability. The bond lengths of these dimer complexes were found to be nearly same as pure complexes C_2_0-C_n. Further, nitrogen (N) atoms were encapsulated inside the secondary cage (C_n) of dimer complexes and the number of N atoms depends on diameter of the cage. The HOMO-LUMO gaps of new proposed complexes indicate the increase in gap as compared to pure complexes. Mulliken charge analysis of these complexes has been studied which shows the significant charge transfer from the N atoms to the secondary cage of these complexes. The study propose the formation of the new dimer complexes which are stable and are able to encapsulate atoms which are otherwise reactive in free space.

Changes in fibrin D-dimer, fibrinogen, and protein S during pregnancy

DEFF Research Database (Denmark)

Hansen, Anette Tarp; Andreasen, Birgitte Horst; Salvig, Jannie Dalby

2010-01-01

Background. Pregnancy is a hypercoagulable state with a 5- to 10- fold higher risk of venous thromboembolism. Existing reference intervals for fibrin D-dimer (D-dimer), functional fibrinogen (fibrinogen) and protein S, free antigen (protein S) are based on non-pregnant patients and reference...... intervals for pregnant patients are warranted. Objectives. The aim of the present study was to contribute to the establishment of reference intervals for D-dimer, fibrinogen and protein S during pregnancy and to discuss the use of the analyses during pregnancy. Methods. We included 55 healthy pregnant women...... in gestational week 11–17, with normal current pregnancy. Blood samples were collected in gestational weeks 11–17, 21–27 and 34–37. The three plasma parameters D-dimer, fibrinogen and protein S were analysed by STA-R Evolution®. Results. A significant rise in D-dimer was found from first to second trimester (p...

Crystallization of the C-terminal domain of the addiction antidote CcdA in complex with its toxin CcdB

International Nuclear Information System (INIS)

Buts, Lieven; De Jonge, Natalie; Loris, Remy; Wyns, Lode; Dao-Thi, Minh-Hoa

2005-01-01

The CcdA C-terminal domain was crystallized in complex with CcdB in two crystal forms that diffract to beyond 2.0 Å resolution. CcdA and CcdB are the antidote and toxin of the ccd addiction module of Escherichia coli plasmid F. The CcdA C-terminal domain (CcdA C36 ; 36 amino acids) was crystallized in complex with CcdB (dimer of 2 × 101 amino acids) in three different crystal forms, two of which diffract to high resolution. Form II belongs to space group P2 1 2 1 2 1 , with unit-cell parameters a = 37.6, b = 60.5, c = 83.8 Å and diffracts to 1.8 Å resolution. Form III belongs to space group P2 1 , with unit-cell parameters a = 41.0, b = 37.9, c = 69.6 Å, β = 96.9°, and diffracts to 1.9 Å resolution

Magnetic properties of a classical XY spin dimer in a “planar” magnetic field

Energy Technology Data Exchange (ETDEWEB)

Ciftja, Orion, E-mail: ogciftja@pvamu.edu [Department of Physics, Prairie View A& M University, Prairie View, TX 77446 (United States); Prenga, Dode [Department of Physics, Faculty of Natural Sciences, University of Tirana, Bul. Zog I, Tirana (Albania)

2016-10-15

Single-molecule magnetism originates from the strong intra-molecular magnetic coupling of a small number of interacting spins. Such spins generally interact very weakly with the neighboring spins in the other molecules of the compound, therefore, inter-molecular spin couplings are negligible. In certain cases the number of magnetically coupled spins is as small as a dimer, a system that can be considered the smallest nanomagnet capable of storing non-trivial magnetic information on the molecular level. Additional interesting patterns arise if the spin motion is confined to a two-dimensional space. In such a scenario, clusters consisting of spins with large-spin values are particularly attractive since their magnetic interactions can be described well in terms of classical Heisenberg XY spins. In this work we calculate exactly the magnetic properties of a nanomagnetic dimer of classical XY spins in a “planar” external magnetic field. The problem is solved by employing a mathematical approach whose idea is the introduction of auxiliary spin variables into the starting expression of the partition function. Results for the total internal energy, total magnetic moment, spin–spin correlation function and zero-field magnetic susceptibility can serve as a basis to understand the magnetic properties of large-spin dimer building blocks. - Highlights: • Exact magnetic properties of a dimer system of classical XY spins in magnetic field. • Partition function in nonzero magnetic field obtained in closed-form. • Novel exact analytic results are important for spin models in a magnetic field. • Result provides benchmarks to gauge the accuracy of computational techniques.

D-dimer: a useful tool in gauging optimal duration of oral anticoagulant therapy?

Directory of Open Access Journals (Sweden)

M. Silingardi

2013-05-01

Full Text Available BACKGROUND AND AIM OF THE STUDY Optimal duration of oral anticoagulant therapy (OAT in idiopathic venous thromboembolism (VTE is unknown. Indefinite OAT carries an unacceptable risk of major bleeding and prospective studies have demonstrated that OAT is no longer protective after its withdrawal. How to identify the patients at risk for recurrence? D-dimer is a marker of thrombin activity. Early prospective studies showed that elevated D-dimer levels after anticoagulation had a highly predictive value for a recurrent episode. Does D-dimer assay have a role in gauging the appropriate duration of anticoagulant therapy? The PROLONG study tries to answer this question. METHOD D-dimer assay was performed one month after stopping anticoagulation. Patiens with normal D-dimer levels did not resume anticoagulation while patients with elevated D-dimer levels were randomized to discontinue or resume anticoagulation. Study end-points was the composite of recurrent VTE and major bleeding during an average follow-up of 1.4 years. RESULTS The rate of recurrence is significantly higher in patients with elevated D-dimer levels who discontinued anticoagulation. Resuming anticoagulation in this cohort of patients markedly reduces recurrent events without increasing major bleeding. DISCUSSION AND CONCLUSIONS PROLONG study is provocative, because D-dimer assay is simple, thus not requiring dedicated laboratory facilities. D-dimer test has otherwise high sensitivity but low specificity in VTE diagnosis. Aspecifically elevated D-dimer levels are available in the elderly and the majority of patients included in the study were > 65 years old, thus introducing a possible selection bias. Nonetheless the results of the study are useful for the clinician. Prolongation of vitamin K antagonists in patients with elevated D-dimer levels one month after discontinuation of OAT for a first unprovoked episode of VTE results in a favourable risk-benefit relationship. Probably this

D-dimer as marker for microcirculatory failure: correlation with LOD and APACHE II scores.

Science.gov (United States)

Angstwurm, Matthias W A; Reininger, Armin J; Spannagl, Michael

2004-01-01

The relevance of plasma d-dimer levels as marker for morbidity and organ dysfunction in severely ill patients is largely unknown. In a prospective study we determined d-dimer plasma levels of 800 unselected patients at admission to our intensive care unit. In 91% of the patients' samples d-dimer levels were elevated, in some patients up to several hundredfold as compared to normal values. The highest mean d-dimer values were present in the patient group with thromboembolic diseases, and particularly in non-survivors of pulmonary embolism. In patients with circulatory impairment (r=0.794) and in patients with infections (r=0.487) a statistically significant correlation was present between d-dimer levels and the APACHE II score (P<0.001). The logistic organ dysfunction score (LOD, P<0.001) correlated with d-dimer levels only in patients with circulatory impairment (r=0.474). On the contrary, patients without circulatory impairment demonstrated no correlation of d-dimer levels to the APACHE II or LOD score. Taking all patients together, no correlations of d-dimer levels with single organ failure or with indicators of infection could be detected. In conclusion, d-dimer plasma levels strongly correlated with the severity of the disease and organ dysfunction in patients with circulatory impairment or infections suggesting that elevated d-dimer levels may reflect the extent of microcirculatory failure. Thus, a therapeutic strategy to improve the microcirculation in such patients may be monitored using d-dimer plasma levels.

Improved anticancer effects of albumin-bound paclitaxel nanoparticle via augmentation of EPR effect and albumin-protein interactions using S-nitrosated human serum albumin dimer.

Science.gov (United States)

Kinoshita, Ryo; Ishima, Yu; Chuang, Victor T G; Nakamura, Hideaki; Fang, Jun; Watanabe, Hiroshi; Shimizu, Taro; Okuhira, Keiichiro; Ishida, Tatsuhiro; Maeda, Hiroshi; Otagiri, Masaki; Maruyama, Toru

2017-09-01

In the latest trend of anticancer chemotherapy research, there were many macromolecular anticancer drugs developed based on enhanced permeability and retention (EPR) effect, such as albumin bound paclitaxel nanoparticle (nab- PTX, also called Abraxane ® ). However, cancers with low vascular permeability posed a challenge for these EPR based therapeutic systems. Augmenting the intrinsic EPR effect with an intrinsic vascular modulator such as nitric oxide (NO) could be a promising strategy. S-nitrosated human serum albumin dimer (SNO-HSA Dimer) shown promising activity previously was evaluated for the synergistic effect when used as a pretreatment agent in nab-PTX therapy against various tumor models. In the high vascular permeability C26 murine colon cancer subcutaneous inoculation model, SNO-HSA Dimer enhanced tumor selectivity of nab-PTX, and attenuated myelosuppression. SNO-HSA Dimer also augmented the tumor growth inhibition of nab-PTX in low vascular permeability B16 murine melanoma subcutaneous inoculation model. Furthermore, nab-PTX therapy combined with SNO-HSA Dimer showed higher antitumor activity and improved survival rate of SUIT2 human pancreatic cancer orthotopic model. In conclusion, SNO-HSA Dimer could enhance the therapeutic effect of nab-PTX even in low vascular permeability or intractable pancreatic cancers. The possible underlying mechanisms of action of SNO-HSA Dimer were discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dimer coverings on random multiple chains of planar honeycomb lattices

International Nuclear Information System (INIS)

Ren, Haizhen; Zhang, Fuji; Qian, Jianguo

2012-01-01

We study dimer coverings on random multiple chains. A multiple chain is a planar honeycomb lattice constructed by successively fusing copies of a ‘straight’ condensed hexagonal chain at the bottom of the previous one in two possible ways. A random multiple chain is then generated by admitting the Bernoulli distribution on the two types of fusing, which describes a zeroth-order Markov process. We determine the expectation of the number of the pure dimer coverings (perfect matchings) over the ensemble of random multiple chains by the transfer matrix approach. Our result shows that, with only two exceptions, the average of the logarithm of this expectation (i.e., the annealed entropy per dimer) is asymptotically nonzero when the fusing process goes to infinity and the length of the hexagonal chain is fixed, though it is zero when the fusing process and the length of the hexagonal chain go to infinity simultaneously. Some numerical results are provided to support our conclusion, from which we can see that the asymptotic behavior fits well to the theoretical results. We also apply the transfer matrix approach to the quenched entropy and reveal that the quenched entropy of random multiple chains has a close connection with the well-known Lyapunov exponent of random matrices. Using the theory of Lyapunov exponents we show that, for some random multiple chains, the quenched entropy per dimer is strictly smaller than the annealed one when the fusing process goes to infinity. Finally, we determine the expectation of the free energy per dimer over the ensemble of the random multiple chains in which the three types of dimers in different orientations are distinguished, and specify a series of non-random multiple chains whose free energy per dimer is asymptotically equal to this expectation. (paper)

A new D-dimer cutoff in bedridden hospitalized elderly patients.

Science.gov (United States)

Granziera, Serena; Rechichi, Alfonsina; De Rui, Marina; De Carlo, Paola; Bertozzo, Giulia; Marigo, Lucia; Nante, Giovanni; Manzato, Enzo

2013-03-01

Asymptomatic deep vein thrombosis (DVT) and pulmonary embolism are leading causes of morbidity following the hospitalization of elderly people. The diagnosis of DVT is supported by the D-dimer laboratory assay. The concentration of D-dimer increases in patients with DVT, but may be high in other conditions too (i.e. cancer, infections and inflammation). Old age coincides with a physiological increase in D-dimer values, and that is why D-dimer assay in the elderly is characteristically highly sensitive but scarcely specific. The aim of our study was to explore the reliability of different D-dimer cutoffs for the diagnosis of asymptomatic DVT in a population of bedridden hospitalized elderly patients. We studied 199 patients who were a mean 86.3 ± 6.7 years old. All participants underwent lower limb Doppler ultrasound (DUS) and D-dimer venous blood sampling on admission. In our cohort, the usual cutoff proved highly sensitive (100%), but its specificity was very poor (20.1%). To find a higher cutoff that could improve the method's specificity, we analyzed our data using a receiver operating characteristic curve analysis. The resulting D-dimer cutoff of 492 μg/l enabled us to retain the same sensitivity while improving the test's specificity to 39.1%, with a consequent improvement in its positive predictive value and accuracy. In addition to improving the method's reliability, this result may be helpful in clinical practice, in both medical wards and nursing homes. By adopting a cutoff of 492 μg/l, clinicians could significantly increase the proportion of older patients in whom DVT can be safely ruled out, reducing referrals for DUS and administration of heparin, with consequent clinical, practical and economic advantages.

Dimerization and DNA-binding of ASR1, a small hydrophilic protein abundant in plant tissues suffering from water loss

International Nuclear Information System (INIS)

Maskin, Laura; Frankel, Nicolas; Gudesblat, Gustavo; Demergasso, Maria J.; Pietrasanta, Lia I.; Iusem, Norberto D.

2007-01-01

The Asr gene family is present in Spermatophyta. Its members are generally activated under water stress. We present evidence that tomato ASR1, one of the proteins of the family, accumulates in seed during late stages of embryogenesis, a physiological process characterized by water loss. In vitro, electrophoretic assays show a homo-dimeric structure for ASR1 and highlight strong non-covalent interactions between monomers prone to self-assemble. Direct visualization of single molecules by atomic force microscopy (AFM) confirms that ASR1 forms homodimers and that uncovers both monomers and dimers bind double stranded DNA

A New Asymmetric ent-Kauranoid Dimer from Rabdosia rubescens

Institute of Scientific and Technical Information of China (English)

LU Hai-ying; LIANG Jing-yu

2012-01-01

Objective To study the ent-kaurane diterpenoids from Rabdosia rubescens.Methods The compounds were isolated by chromatographies and their structures were identified by spectral analyses.Results Four compounds were isolated,and they were identified as bisrubescensin E (1),2α,3α,24-trihydroxyurs-12-en-28-oic acid (2),2α,3α,24-trihydroxyurs-12,20-(30)-dien-28-oic acid (3),and 6,7-dihydroxycoumarin (4).Conclusion Compound 1 is a new asymmetric ent-kauranoid dimer.Compound 2 is isolated from the plant for the first time.Compounds 3 and 4 are isolated from the plants ofRabdosia (B1.) Hassk for the first time.

Mutational analysis of TRAF6 reveals a conserved functional role of the RING dimerization interface and a potentially necessary but insufficient role of RING-dependent TRAF6 polyubiquitination towards NF-κB activation.

Science.gov (United States)

Megas, Charilaos; Hatzivassiliou, Eudoxia G; Yin, Qian; Marinopoulou, Elli; Hadweh, Paul; Vignali, Dario A A; Mosialos, George

2011-05-01

TRAF6 is an E3 ubiquitin ligase that plays a pivotal role in the activation of NF-κB by innate and adaptive immunity stimuli. TRAF6 consists of a highly conserved carboxyl terminal TRAF-C domain which is preceded by a coiled coil domain and an amino terminal region that contains a RING domain and a series of putative zinc-finger motifs. The TRAF-C domain contributes to TRAF6 oligomerization and mediates the interaction of TRAF6 with upstream signaling molecules whereas the RING domain comprises the core of the ubiquitin ligase catalytic domain. In order to identify structural elements that are important for TRAF6-induced NF-κB activation, mutational analysis of the TRAF-C and RING domains was performed. Alterations of highly conserved residues of the TRAF-C domain of TRAF6 did not affect significantly the ability of the protein to activate NF-κB. On the other hand a number of functionally important residues (L77, Q82, R88, F118, N121 and E126) for the activation of NF-κB were identified within the RING domain of TRAF6. Interestingly, several homologues of these residues in TRAF2 were shown to have a conserved functional role in TRAF2-induced NF-κB activation and lie at the dimerization interface of the RING domain. Finally, whereas alteration of Q82, R88 and F118 compromised both the K63-linked polyubiquitination of TRAF6 and its ability to activate NF-κB, alteration of L77, N121 and E126 diminished the NF-κB activating function of TRAF6 without affecting TRAF6 K63-linked polyubiquitination. Our results support a conserved functional role of the TRAF RING domain dimerization interface and a potentially necessary but insufficient role for RING-dependent TRAF6 K63-linked polyubiquitination towards NF-κB activation in cells. Copyright © 2010 Elsevier Inc. All rights reserved.

A complete assignment of the vibrational spectra of 2-furoic acid based on the structures of the more stable monomer and dimer

Science.gov (United States)

Ghalla, Houcine; Issaoui, Noureddine; Castillo, María Victoria; Brandán, Silvia Antonia; Flakus, Henryk T.

2014-03-01

The structural and vibrational properties of cyclic dimer of 2-furoic acid (2FA) were predicted by combining the available experimental infrared and Raman spectra in the solid phase and ab initio calculations based on density functional theory (DFT) with Pople's basis sets. The calculations show that there are two cyclic dimers for the title molecule that have been theoretically determined in the gas phase, and that only one of them, cis conformer, is present in the solid phase. The complete assignment of the 66 normal vibrational modes for the cis cyclic dimer was performed using the Pulay's Scaled Quantum Mechanics Force Field (SQMFF) methodology. Four strong bands in the infrared spectrum at 1583, 1427, 1126 and 887 cm-1 and the group of bands in the Raman spectrum at 1464, 1452, 1147, 1030, 885, 873, 848, 715 and 590 cm-1 are characteristic of the dimeric form of 2FA in the solid phase. In this work, the calculated structural and vibrational properties of both dimeric species were analyzed and compared between them. In addition, three types of atomic charges, bond orders, possible charge transfer, topological properties of the furan rings, Natural Bond Orbital (NBO) and Atoms in Molecules (AIM) theory calculations were employed to study the stabilities and intermolecular interactions of the both dimers of 2FA.

On the asymptotics of dimers on tori

OpenAIRE

Kenyon, Richard W.; Sun, Nike; Wilson, David B.

2013-01-01

We study asymptotics of the dimer model on large toric graphs. Let $\\mathbb L$ be a weighted $\\mathbb{Z}^2$-periodic planar graph, and let $\\mathbb{Z}^2 E$ be a large-index sublattice of $\\mathbb{Z}^2$. For $\\mathbb L$ bipartite we show that the dimer partition function on the quotient $\\mathbb{L}/(\\mathbb{Z}^2 E)$ has the asymptotic expansion $\\exp[A f_0 + \\text{fsc} + o(1)]$, where $A$ is the area of $\\mathbb{L}/(\\mathbb{Z}^2 E)$, $f_0$ is the free energy density in the bulk, and $\\text{fsc...

On the diffusion and self-trapping of surface dimers

Science.gov (United States)

Kappus, W.

1982-03-01

The theory of elastic interactions between surface atoms which are caused by substrate strains is applied to the interaction of dimers on the (211) surface of tungsten. From the comparison of theoretical and experimental interactions which were derived from the diffusion behaviour of dimers, conclusions are drawn on the nature of the adatom-substrate bond.

Bacterial actin MreB forms antiparallel double filaments.

Science.gov (United States)

van den Ent, Fusinita; Izoré, Thierry; Bharat, Tanmay Am; Johnson, Christopher M; Löwe, Jan

2014-05-02

Filaments of all actin-like proteins known to date are assembled from pairs of protofilaments that are arranged in a parallel fashion, generating polarity. In this study, we show that the prokaryotic actin homologue MreB forms pairs of protofilaments that adopt an antiparallel arrangement in vitro and in vivo. We provide an atomic view of antiparallel protofilaments of Caulobacter MreB as apparent from crystal structures. We show that a protofilament doublet is essential for MreB's function in cell shape maintenance and demonstrate by in vivo site-specific cross-linking the antiparallel orientation of MreB protofilaments in E. coli. 3D cryo-EM shows that pairs of protofilaments of Caulobacter MreB tightly bind to membranes. Crystal structures of different nucleotide and polymerisation states of Caulobacter MreB reveal conserved conformational changes accompanying antiparallel filament formation. Finally, the antimicrobial agents A22/MP265 are shown to bind close to the bound nucleotide of MreB, presumably preventing nucleotide hydrolysis and destabilising double protofilaments.DOI: http://dx.doi.org/10.7554/eLife.02634.001. Copyright © 2014, van den Ent et al.

Explicit correlation treatment of the potential energy surface of CO{sub 2} dimer

Energy Technology Data Exchange (ETDEWEB)

Kalugina, Yulia N., E-mail: kalugina@phys.tsu.ru [Tomsk State University, 36 Lenin Ave., Tomsk 634050 (Russian Federation); Buryak, Ilya A. [Obukhov Institute of Atmospheric Physics, Russian Academy of Sciences, Moscow (Russian Federation); Chemistry Department, Lomonosov Moscow State University, Moscow (Russian Federation); Ajili, Yosra [Université Paris-Est, Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, 5 Bd Descartes, 77454 Marne-La-Vallée (France); Laboratoire de Spectroscopie Atomique, Moléculaire et Applications - LSAMA Université de Tunis El Manar (Tunisia); Vigasin, Andrei A. [Obukhov Institute of Atmospheric Physics, Russian Academy of Sciences, Moscow (Russian Federation); Jaidane, Nejm Eddine [Laboratoire de Spectroscopie Atomique, Moléculaire et Applications - LSAMA Université de Tunis El Manar (Tunisia); Hochlaf, Majdi [Université Paris-Est, Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208 CNRS, 5 Bd Descartes, 77454 Marne-La-Vallée (France)

2014-06-21

We present an extensive study of the four-dimensional potential energy surface (4D-PES) of the carbon dioxide dimer, (CO{sub 2}){sub 2}. This PES is developed over the set of intermolecular coordinates. The electronic computations are carried out at the explicitly correlated coupled cluster method with single, double, and perturbative triple excitations [CCSD(T)-F12] level of theory in connection with the augmented correlation-consistent aug-cc-pVTZ basis set. An analytic representation of the 4D-PES is derived. Our extensive calculations confirm that “Slipped Parallel” is the most stable form and that the T-shaped structure corresponds to a transition state. Later on, this PES is employed for the calculations of the vibrational energy levels of the dimer. Moreover, the temperature dependence of the dimer second virial coefficient and of the first spectral moment of rototranslational collision-induced absorption spectrum is derived. For both quantities, a good agreement is found between our values and the experimental data for a wide range of temperatures. This attests to the high quality of our PES. Generally, our PES and results can be used for modeling CO{sub 2} supercritical fluidity and examination of its role in planetary atmospheres. It can be also incorporated into dynamical computations of CO{sub 2} capture and sequestration. This allows deep understanding, at the microscopic level, of these processes.

Selective ligand activity at Nur/retinoid X receptor complexes revealed by dimer-specific bioluminescence resonance energy transfer-based sensors

Science.gov (United States)

Giner, Xavier C; Cotnoir-White, David; Mader, Sylvie; Lévesque, Daniel

2017-01-01

Retinoid X receptors (RXR) play a role as master regulators due to their capacity to form heterodimers with other nuclear receptors. Accordingly, retinoid signaling is involved in multiple biological processes, including development, cell differentiation, metabolism and cell death. However, the role and functions of RXR in different heterodimer complexes remain unsolved, mainly because most RXR drugs (called rexinoids) are not selective to specific heterodimer complexes. This also strongly limits the use of rexinoids for specific therapeutic approaches. In order to better characterize rexinoids at specific nuclear receptor complexes, we have developed and optimized luciferase protein complementation-based Bioluminescence Resonance Energy Transfer (BRET) assays, which can directly measure recruitment of a co-activator motif fused to yellow fluorescent protein (YFP) by specific nuclear receptor dimers. To validate the assays, we compared rexinoid modulation of co-activator recruitment by RXR homodimer, and heterodimers Nur77/RXR and Nurr1/RXR. Results reveal that some rexinoids display selective co-activator recruitment activities with homo- or hetero-dimer complexes. In particular, SR11237 (BMS649) has increased potency for recruitment of co-activator motif and transcriptional activity with the Nur77/RXR heterodimer compared to other complexes. This technology should prove useful to identify new compounds with specificity for individual dimeric species formed by nuclear receptors. PMID:26148973

Photorepair and excision repair removal of UV-induced pyrimidine dimers and (6-4) photoproducts in the tail fin of the Medaka, Oryzias latipes

International Nuclear Information System (INIS)

Funayama, Tomoo; Mitani, Hiroshi; Shima, Akihiro; Ishigaki, Yasuhito; Matsunaga, Tsukasa; Nikaido, Osamu.

1994-01-01

Induction and repair of UV-B induced DNA damage in the tail fin of the Medaka, were examined immunohistochemically and by the enzyme-linked immunosorbent assay (ELISA). UV-induced DNA damage was detected only in the outermost layer of epithelial cells and did not differ in fishes having different degree of melanization. Both pyrimidine dimers and (6-4) photoproducts in the fin cells were removed by excision repair in the dark, the excision of (6-4) photoproducts being about twice as efficient as that of pyrimidine dimers. The rate of excision repair of UV-induced lesions in fin tissue was three to four times that in cultured Medaka cells, OL32.. In the fin cells, reductions in the numbers of pyrimidine dimers and (6-4) photoproducts were seen after treatment with fluorescent light, whereas less reductions of pyrimidine dimers and no reductions of (6-4) photoproducts were observed in OL32 cells. (author)

The 18-kilodalton Chlamydia trachomatis histone H1-like protein (Hc1) contains a potential N-terminal dimerization site and a C-terminal nucleic acid-binding domain

DEFF Research Database (Denmark)

Pedersen, LB; Birkelund, Svend; Holm, A

1996-01-01

The Chlamydia trachomatis histone H1-like protein (Hc1) is a DNA-binding protein specific for the metabolically inactive chlamydial developmental form, the elementary body. Hc1 induces DNA condensation in Escherichia coli and is a strong inhibitor of transcription and translation. These effects may......-hydroxysuccinimide ester), purified recombinant Hc1 was found to form dimers. The dimerization site was located in the N-terminal part of Hc1 (Hc1(2-57)). Moreover, circular dichroism measurements indicated an overall alpha-helical structure of this region. By using limited proteolysis, Southwestern blotting, and gel...

SHAPE analysis of the FIV Leader RNA reveals a structural switch potentially controlling viral packaging and genome dimerization.

Science.gov (United States)

Kenyon, Julia C; Tanner, Sian J; Legiewicz, Michal; Phillip, Pretty S; Rizvi, Tahir A; Le Grice, Stuart F J; Lever, Andrew M L

2011-08-01

Feline immunodeficiency virus (FIV) infects many species of cat, and is related to HIV, causing a similar pathology. High-throughput selective 2' hydroxyl acylation analysed by primer extension (SHAPE), a technique that allows structural interrogation at each nucleotide, was used to map the secondary structure of the FIV packaging signal RNA. Previous studies of this RNA showed four conserved stem-loops, extensive long-range interactions (LRIs) and a small, palindromic stem-loop (SL5) within the gag open reading frame (ORF) that may act as a dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Our analyses of wild-type (wt) and mutant RNAs suggest that although the four conserved stem-loops are static structures, the 5' and 3' regions previously shown to form LRI also adopt an alternative, yet similarly conserved conformation, in which the putative DIS is occluded, and which may thus favour translational and splicing functions over encapsidation. SHAPE and in vitro dimerization assays were used to examine SL5 mutants. Dimerization contacts appear to be made between palindromic loop sequences in SL5. As this stem-loop is located within the gag ORF, recognition of a dimeric RNA provides a possible mechanism for the specific packaging of genomic over spliced viral RNAs.

The crystal structure of an intermediate dimer of aspergilloglutamic peptidase that mimics the enzyme-activation product complex produced upon autoproteolysis.

Science.gov (United States)

Sasaki, Hiroshi; Kubota, Keiko; Lee, Woo C; Ohtsuka, Jun; Kojima, Masaki; Iwata, So; Nakagawa, Atsushi; Takahashi, Kenji; Tanokura, Masaru

2012-07-01

Aspergilloglutamic peptidase from Aspergillus niger var. macrosporus (AGP) is one of the so-called pepstatin-insensitive acid endopeptidases, which are distinct from the well-studied aspartic peptidases. Among the known homologues of the glutamic peptidases, AGP is a unique two-chain enzyme with a light chain and a heavy chain bound non-covalently with each other, and thus is an interesting target for protein structure-function relationship studies. In this article, we report the crystal structure of a dimeric form of the enzyme at a resolution of 1.6 Å. This form has a unique structure in which the C-terminal region of the light chain of one of the molecules binds to the active site cleft of the other molecule like a part of a substrate. This form mimics the enzyme-activation product complex produced upon autoproteolysis, and provides a structural clue that could help to clarify the activation mechanism. This type of dimeric structure of a peptidase is here reported for the first time.

Asymmetric monometallic nanorod nanoparticle dimer and related compositions and methods

KAUST Repository

Han, Yu; Huang, Jianfeng; Zhu, Yihan

2016-01-01

and three-dimensional morphology of the dimer, as well as the growth pathway of the AuNP on the AuNR seed, was investigated for this example. The dimer exhibits an extraordinary broadband optical extinction spectrum spanning the UV, visible, and near

Kinetics and Thermodynamics of Watson-Crick Base Pairing Driven DNA Origami Dimerization.

Science.gov (United States)

Zenk, John; Tuntivate, Chanon; Schulman, Rebecca

2016-03-16

We investigate the kinetics and thermodynamics of DNA origami dimerization using flat rectangle origami components and different architectures of Watson-Crick complementary single-stranded DNA ("sticky end") linking strategies. We systematically vary the number of linkers, the length of the sticky ends on the linker, and linker architecture and measure the corresponding yields as well as forward and reverse reaction rate constants through fluorescence quenching assays. Yields were further verified using atomic force microscopy. We calculate values of H° and ΔS° for various interface designs and find nonlinear van't Hoff behavior, best described by two linear equations, suggesting distinct regimes of dimerization between those with and those without well-formed interfaces. We find that self-assembly reactions can be tuned by manipulating the interface architecture without suffering a loss in yield, even when yield is high, ∼75-80%. We show that the second-order forward reaction rate constant (k(on)) depends on both linker architecture and number of linkers used, with typical values on the order of 10(5)-10(6) (M·s)(-1), values that are similar to those of bimolecular association of small, complementary DNA strands. The k(on) values are generally non-Arrhenius, tending to increase with decreasing temperature. Finally, we use kinetic and thermodynamic information about the optimal linking architecture to extend the system to an infinite, two-component repeating lattice system and show that we can form micron-sized lattices, with well-formed structures up to 8 μm(2).

DFT Study of dimers of dimethyl sulfoxide in gas phase

Directory of Open Access Journals (Sweden)

Reza Fazaeli

2014-10-01

Full Text Available Density functional (DFT calculations at M05-2x/aug-cc-pVDZ level were used to analyze the interactions between dimethyl sulfoxide (DMSO dimers. The structures obtained have been ana-lyzed with the Atoms in Molecules (AIMs and Natural Bond Orbital (NBO methodologies. Four minima were located on the potential energy surface of the dimers. Three types of interac-tions are observed, CH•••O, CH•••S hydrogen bonds and orthogonal interaction between the lone pair of the oxygen with the electron-deficient region of the sulfur atom. Stabilization energies of dimers including BSSE and ZPE are in the range 27–40 kJmol-1. The most stable conformers of dimers at DFT level is cyclic structure with antiparallel orientation of S=O groups pairing with three C–H∙∙∙O and a S∙∙∙O interactions.

Visualization of multipolar longitudinal and transversal surface plasmon modes in nanowire dimers.

Science.gov (United States)

Alber, Ina; Sigle, Wilfried; Müller, Sven; Neumann, Reinhard; Picht, Oliver; Rauber, Markus; van Aken, Peter A; Toimil-Molares, Maria Eugenia

2011-12-27

We study the transversal and longitudinal localized surface plasmon resonances in single nanowires and nanowire dimers excited by the fast traveling electron beam in a transmission electron microscope equipped with high-resolution electron energy-loss spectroscopy. Bright and dark longitudinal modes up to the fifth order are resolved on individual metallic nanowires. On nanowire dimers, mode splitting into bonding and antibonding is measured up to the third order for several dimers with various aspect ratio and controlled gap size. We observe that the electric field maxima of the bonding modes are shifted toward the gap, while the electric field maxima of the antibonding modes are shifted toward the dimer ends. Finally, we observe that the transversal mode is not detected in the region of the dimer gap and decays away from the rod more rapidly than the longitudinal modes.

Accuracy of D-Dimers to Rule Out Venous Thromboembolism Events across Age Categories

Directory of Open Access Journals (Sweden)

G. Der Sahakian

2010-01-01

Full Text Available Background. Strategies combining pretest clinical assessment and D-dimers measurement efficiently and safely rule out venous thromboembolism events (VTE in low- and intermediate-risk patients. Objectives. As process of ageing is associated with altered concentrations of coagulation markers including an increase in D-dimers levels, we investigated whether D-dimers could reliably rule out VTE across age categories. Method. We prospectively assessed the test performance in 1,004 patients visiting the emergency department during the 6-month period with low or intermediate risk of VTE who also received additional diagnostic procedures. Results. 67 patients had VTE with D-dimers levels above the threshold, and 3 patients displayed D-dimers levels below the threshold. We observed that specificity of D-dimers test decreased in an age-dependent manner. However, sensitivity and negative predictive value remained at very high level in each age category including older patients. Conclusion. We conclude that, even though D-dimers level could provide numerous false positive results in elderly patients, its high sensitivity could reliably help physicians to exclude the diagnosis of VTE in every low- and intermediate-risk patient.

46 CFR 308.529 - Surety Bond B, Form MA-309.

Science.gov (United States)

2010-10-01

... Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.529 Surety Bond B, Form MA-309. An Assured who elects to substitute a surety bond for a collateral deposit fund shall submit Form MA-309...

Data on the effect of in vivo knockdown using artificial ErbB3 miRNA on Remak bundle structure

Directory of Open Access Journals (Sweden)

Yuki Miyamoto

2017-06-01

Full Text Available Mature Schwann cells, the peripheral nervous system (PNS glial cells, have two major roles for neuronal axons (Bunge, 1993 [1]. For large diameter axons, Schwann cells form myelin sheaths with multiple layers. For small diameter axons, they form Remak bundle composed only of single layer of the Schwann cell plasma membrane. In the PNS, ErbB3 forms a dimer with ErbB2 on the Schwann cell plasma membrane. ErbB3 plays a key role in myelination by myelinating Schwann cells, that is to say, its role in myelin thickness. Herein we provide the data regarding the effect of in vivo knockdown of ErbB3 on the thickness between an axon and a neighboring axon in Remak bundle, which is formed by non-myelinating Schwann cells. Since ErbB3 knockout mice are embryonically lethal, Schwann cell lineage-specific transgenic mice transcribing ErbB3 shRNA with an artificial miRNA backbone were generated and used in these experiments (Torii et al., 2014 [2].

Analysis of pyrimidine dimer content of isolated DNA by nuclease digestion

International Nuclear Information System (INIS)

Farland, W.H.; Sutherland, B.M.

1980-01-01

Isolated DNA is highly susceptible to degradation by exogenous nucleases. Complete digestion is possible with a number of well-characterized enzymes from a variety of sources. Treatment of DNA with a battery of enzymes including both phosphodiesterase and phosphatase activities yields a mixture of nucleosides and inorganic phosphate (P/sub i/) as a final product. Unlike native DNA, ultraviolet-irradiated DNA is resistant to complete digestion. Setlow et al. demonstrated that the structural changes in the DNA responsible for the nuclease resistance were the formation of cyclobutyl pyrimidine dimers, the major photoproduct in UV-irradiated DNA. Using venom phosphodiesterase, they demonstrated that UV irradiation of DNA affected both the rate and extent of enzymatic hydrolysis. In addition, it was demonstrated that the major nuclease-resistant product of this hydrolysis was an oligonucleotide containing dimerized pyrimidines. Treatment of the DNA to split the dimers, either photochemically or photoenzymatically, rendered the polymer more susceptible to hydrolysis by the phosphodiesterase. The specificity of photoreactivating enzyme for pyrimidine dimers lends support to the role of these structures in conferring nuclease resistance to UV-irradiated DNA. The nuclease resistance of DNA containing dimers has been the basis of several assays for the measurement of these photoproducts. Sutherland and Chamberlin reported the development of a rapid and sensitive assay for dimers in 32 P-labeled DNA

Prednisolone-induced differential gene expression in mouse liver carrying wild type or a dimerization-defective glucocorticoid receptor

Directory of Open Access Journals (Sweden)

Dokter Wim

2010-06-01

Full Text Available Abstract Background Glucocorticoids (GCs control expression of a large number of genes via binding to the GC receptor (GR. Transcription may be regulated either by binding of the GR dimer to DNA regulatory elements or by protein-protein interactions of GR monomers with other transcription factors. Although the type of regulation for a number of individual target genes is known, the relative contribution of both mechanisms to the regulation of the entire transcriptional program remains elusive. To study the importance of GR dimerization in the regulation of gene expression, we performed gene expression profiling of livers of prednisolone-treated wild type (WT and mice that have lost the ability to form GR dimers (GRdim. Results The GR target genes identified in WT mice were predominantly related to glucose metabolism, the cell cycle, apoptosis and inflammation. In GRdim mice, the level of prednisolone-induced gene expression was significantly reduced compared to WT, but not completely absent. Interestingly, for a set of genes, involved in cell cycle and apoptosis processes and strongly related to Foxo3a and p53, induction by prednisolone was completely abolished in GRdim mice. In contrast, glucose metabolism-related genes were still modestly upregulated in GRdim mice upon prednisolone treatment. Finally, we identified several novel GC-inducible genes from which Fam107a, a putative histone acetyltransferase complex interacting protein, was most strongly dependent on GR dimerization. Conclusions This study on prednisolone-induced effects in livers of WT and GRdim mice identified a number of interesting candidate genes and pathways regulated by GR dimers and sheds new light onto the complex transcriptional regulation of liver function by GCs.

DNA binding polarity, dimerization, and ATPase ring remodeling in the CMG helicase of the eukaryotic replisome

Science.gov (United States)

Costa, Alessandro; Renault, Ludovic; Swuec, Paolo; Petojevic, Tatjana; Pesavento, James J; Ilves, Ivar; MacLellan-Gibson, Kirsty; Fleck, Roland A; Botchan, Michael R; Berger, James M

2014-01-01

The Cdc45/Mcm2-7/GINS (CMG) helicase separates DNA strands during replication in eukaryotes. How the CMG is assembled and engages DNA substrates remains unclear. Using electron microscopy, we have determined the structure of the CMG in the presence of ATPγS and a DNA duplex bearing a 3′ single-stranded tail. The structure shows that the MCM subunits of the CMG bind preferentially to single-stranded DNA, establishes the polarity by which DNA enters into the Mcm2-7 pore, and explains how Cdc45 helps prevent DNA from dissociating from the helicase. The Mcm2-7 subcomplex forms a cracked-ring, right-handed spiral when DNA and nucleotide are bound, revealing unexpected congruencies between the CMG and both bacterial DnaB helicases and the AAA+ motor of the eukaryotic proteasome. The existence of a subpopulation of dimeric CMGs establishes the subunit register of Mcm2-7 double hexamers and together with the spiral form highlights how Mcm2-7 transitions through different conformational and assembly states as it matures into a functional helicase. DOI: http://dx.doi.org/10.7554/eLife.03273.001 PMID:25117490

Dimerization of a Viral SET Protein Endows its Function

Energy Technology Data Exchange (ETDEWEB)

H Wei; M Zhou

2011-12-31

Histone modifications are regarded as the most indispensible phenomena in epigenetics. Of these modifications, lysine methylation is of the greatest complexity and importance as site- and state-specific lysine methylation exerts a plethora of effects on chromatin structure and gene transcription. Notably, paramecium bursaria chlorella viruses encode a conserved SET domain methyltransferase, termed vSET, that functions to suppress host transcription by methylating histone H3 at lysine 27 (H3K27), a mark for eukaryotic gene silencing. Unlike mammalian lysine methyltransferases (KMTs), vSET functions only as a dimer, but the underlying mechanism has remained elusive. In this study, we demonstrate that dimeric vSET operates with negative cooperativity between the two active sites and engages in H3K27 methylation one site at a time. New atomic structures of vSET in the free form and a ternary complex with S-adenosyl homocysteine and a histone H3 peptide and biochemical analyses reveal the molecular origin for the negative cooperativity and explain the substrate specificity of H3K27 methyltransferases. Our study suggests a 'walking' mechanism, by which vSET acts all by itself to globally methylate host H3K27, which is accomplished by the mammalian EZH2 KMT only in the context of the Polycomb repressive complex.

Type B activity limits for air transport - (an examination of special form and non-special form limits)

International Nuclear Information System (INIS)

Eyre, P.

2004-01-01

This paper examines the application of the ''Q system'' with respect to the maximum limits of activity permitted in Type B (Type B(U) or Type B(M)) packages when transported by air. In particular, estimation is made of the radiological consequences to determine if there is a difference depending on whether the material is in special form or not. An estimate is also made of the radiological consequences of an air accident involving low dispersible radioactive material (LDRM) in the reference Type B package

Pyrimidine dimer sites associated with the daughter DNA strands in uv-irradiated human fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Lehmann, A R; Kirk-Bell, S [Sussex Univ., Brighton (UK)

1978-03-01

Pyrimidine dimer sites associated with the newly-synthesized DNA were detected during post-replication repair of DNA in uv-irradiated human fibroblasts. These pyrimidine dimer sites were inferred from a decrease in the molecular weight of pulse-labelled DNA after treatment with an extract of Micrococcus luteus containing uv-specific endonuclease activity. In DNA synthesized immediately after irradiation, the frequency of these daughter strand dimer sites was 7 to 20% of that in the parental DNA. Such sites were found in fibroblasts from normal donors and from xeroderma pigmentosum patients (with defects in excision-repair or post-replication repair). They were excised from the DNA of normal cells. As the time between uv irradiation and pulse-labelling was increased, the frequency of dimer sites associated with the labelled DNA decreased. If the pulse-label was delivered 6 h after irradiation of normal cells or excision-defective xeroderma pigmentosum cells, no dimer sites were detected in the labelled DNA. It has usually been assumed that daughter-strand dimer sites were the result of recombinational exchanges. The assay procedure used in these experiments and in similar experiments of others did not distinguish between labelled DNA containing pyrimidine dimers within the labelled section, and labelled DNA which did not contain pyrimidine dimers but was attached to unlabelled DNA which did contain dimers. The latter structures would arise during normal replication immediately following uv irradiation of mammalian cells. Calculations are presented which suggest that a significant proportion and conceivably all of the dimer sites associated with the daughter strands may have arisen in this way, rather than from recombinational exchanges as has been generally assumed.

Pyrimidine dimer sites associated with the daughter DNA strands in UV-irradiated human fibroblasts

International Nuclear Information System (INIS)

Lehmann, A.R.; Kirk-Bell, S.

1978-01-01

Pyrimidine dimer sites associated with the newly-synthesized DNA were detected during post-replication repair of DNA in UV-irradiated human fibroblasts. These pyrimidine dimer sites were inferred from a decrease in the molecular weight of pulse-labelled DNA after treatment with an extract of Micrococcus luteus containing UV-specific endonuclease activity. In DNA synthesized immediately after irradiation the frequency of these daughter strand dimer sites was 7-20% of that in the parental DNA. Such sites were found in fibroblasts from normal donors and from xeroderma pigmentosum patients (with defects in excision-repair or post-replication repair). They were excised from the DNA of normal cells. As the time between UV-irradiation and pulse-labelling was increased, the frequency of dimer sites associated with the labelled DNA decreased. If the pulse-label was delivered 6 h after irradiation of normal cells or excision-defective xeroderma pigmentosum cells, no dimer sites were detected in the labelled DNA. It has usually been assumed that daughter-strand dimer sites were the result of recombinational exchanges. The assay procedure used in these experiments and in similar experiments of others did not distinguish between labelled DNA containing pyrimidine dimers within the labelled section, and labelled DNA which did not contain pyrimidine dimers but was attached to unlabelled DNA which did contain dimers. The latter structures would arise during normal replication immediately following UV-irradiation of mammalian cells. Calculations are presented which suggest that a significant proportion and conceivably all of the dimer sites associated with the daughter strands may have arisen in this way, rather than from recombinational exchanges as has been generally assumed. (author)

Single-Molecule Rotational Switch on a Dangling Bond Dimer Bearing.

Science.gov (United States)

Godlewski, Szymon; Kawai, Hiroyo; Kolmer, Marek; Zuzak, Rafał; Echavarren, Antonio M; Joachim, Christian; Szymonski, Marek; Saeys, Mark

2016-09-27

One of the key challenges in the construction of atomic-scale circuits and molecular machines is to design molecular rotors and switches by controlling the linear or rotational movement of a molecule while preserving its intrinsic electronic properties. Here, we demonstrate both the continuous rotational switching and the controlled step-by-step single switching of a trinaphthylene molecule adsorbed on a dangling bond dimer created on a hydrogen-passivated Ge(001):H surface. The molecular switch is on-surface assembled when the covalent bonds between the molecule and the dangling bond dimer are controllably broken, and the molecule is attached to the dimer by long-range van der Waals interactions. In this configuration, the molecule retains its intrinsic electronic properties, as confirmed by combined scanning tunneling microscopy/spectroscopy (STM/STS) measurements, density functional theory calculations, and advanced STM image calculations. Continuous switching of the molecule is initiated by vibronic excitations when the electrons are tunneling through the lowest unoccupied molecular orbital state of the molecule. The switching path is a combination of a sliding and rotation motion over the dangling bond dimer pivot. By carefully selecting the STM conditions, control over discrete single switching events is also achieved. Combined with the ability to create dangling bond dimers with atomic precision, the controlled rotational molecular switch is expected to be a crucial building block for more complex surface atomic-scale devices.

Spin Quantum Tunneling via Entangled States in a Dimer of Exchange-Coupled Single-Molecule Magnets

Science.gov (United States)

Tiron, R.; Wernsdorfer, W.; Foguet-Albiol, D.; Aliaga-Alcalde, N.; Christou, G.

2003-11-01

A new family of supramolecular, antiferromagnetically exchange-coupled dimers of single-molecule magnets (SMMs) has recently been reported. Each SMM acts as a bias on its neighbor, shifting the quantum tunneling resonances of the individual SMMs. Hysteresis loop measurements on a single crystal of SMM dimers have now established quantum tunneling of the magnetization via entangled states of the dimer. This shows that the dimer really does behave as a quantum mechanically coupled dimer, and also allows the measurement of the longitudinal and transverse superexchange coupling constants.

Oligomeric forms of the metastasis-related Mts1 (S100A4) protein stimulate neuronal differentiation in cultures of rat hippocampal neurons

DEFF Research Database (Denmark)

Novitskaya, V; Grigorian, M; Kriajevska, M

2000-01-01

protein family. The oligomeric but not the dimeric form of Mts1 strongly induces differentiation of cultured hippocampal neurons. A mutant with a single Y75F amino acid substitution, which stabilizes the dimeric form of Mts1, is unable to promote neurite extension. Disulfide bonds do not play an essential...

Structure-Function Model for Kissing Loop Interactions That Initiate Dimerization of Ty1 RNA

Directory of Open Access Journals (Sweden)

Eric R. Gamache

2017-04-01

Full Text Available The genomic RNA of the retrotransposon Ty1 is packaged as a dimer into virus-like particles. The 5′ terminus of Ty1 RNA harbors cis-acting sequences required for translation initiation, packaging and initiation of reverse transcription (TIPIRT. To identify RNA motifs involved in dimerization and packaging, a structural model of the TIPIRT domain in vitro was developed from single-nucleotide resolution RNA structural data. In general agreement with previous models, the first 326 nucleotides of Ty1 RNA form a pseudoknot with a 7-bp stem (S1, a 1-nucleotide interhelical loop and an 8-bp stem (S2 that delineate two long, structured loops. Nucleotide substitutions that disrupt either pseudoknot stem greatly reduced helper-Ty1-mediated retrotransposition of a mini-Ty1, but only mutations in S2 destabilized mini-Ty1 RNA in cis and helper-Ty1 RNA in trans. Nested in different loops of the pseudoknot are two hairpins with complementary 7-nucleotide motifs at their apices. Nucleotide substitutions in either motif also reduced retrotransposition and destabilized mini- and helper-Ty1 RNA. Compensatory mutations that restore base-pairing in the S2 stem or between the hairpins rescued retrotransposition and RNA stability in cis and trans. These data inform a model whereby a Ty1 RNA kissing complex with two intermolecular kissing-loop interactions initiates dimerization and packaging.

Quantitative determination of cyclobutane thymine dimers in DNA by stable isotope-dilution mass spectrometry

International Nuclear Information System (INIS)

Podmore, I.D.; Cooke, M.S.; Herbert, K.E.; Lunec, J.

1996-01-01

In order to understand the role of UV-induced DNA lesions in biological processes such as mutagenesis and carcinogenesis, it is essential to detect and quantify DNA damage in cells. In this paper we present a novel and both highly selective and sensitive assay using capillary gas chromatography (GC) combined with mass spectrometry (MS) for the detection and accurate quantitation of a major product of UV-induced DNA damage (cis-syb cyclobutadithymine). Quantitation of the cyclobutane thymine dimer was achieved by the use of an internal standard in the form of a stable 2 H-labeled analogue. Both isotopically labeled and nonlabeled dimers were prepared directly from their corresponding monomers. Each was identified as their trimethylsilyl ether derivative by GC-MS. Calibration plots were obtained for known quantities of both nonlabeled and analyte and internal standard. Quantitation of cis-syn cyclobutadithymine was demonstrated in DNA exposed to UVC radiation over a dose range of 0 3500 J m -2 . Under the conditions used, the limit of detection was found to be 20-50 fmol on column (equivalent to 0.002-0.005 nmol dimer per mg DNA). The results of the present study indicate that capillary GC-MS is an ideally suited technique for selective and sensitive quantification of cis-syn cyclobutadithymine in DNA and hence UV-induced DNA damage. (author)

New Insights into Molecular Organization of Human Neuraminidase-1: Transmembrane Topology and Dimerization Ability

Science.gov (United States)

Maurice, Pascal; Baud, Stéphanie; Bocharova, Olga V.; Bocharov, Eduard V.; Kuznetsov, Andrey S.; Kawecki, Charlotte; Bocquet, Olivier; Romier, Beatrice; Gorisse, Laetitia; Ghirardi, Maxime; Duca, Laurent; Blaise, Sébastien; Martiny, Laurent; Dauchez, Manuel; Efremov, Roman G.; Debelle, Laurent

2016-12-01

Neuraminidase 1 (NEU1) is a lysosomal sialidase catalyzing the removal of terminal sialic acids from sialyloconjugates. A plasma membrane-bound NEU1 modulating a plethora of receptors by desialylation, has been consistently documented from the last ten years. Despite a growing interest of the scientific community to NEU1, its membrane organization is not understood and current structural and biochemical data cannot account for such membrane localization. By combining molecular biology and biochemical analyses with structural biophysics and computational approaches, we identified here two regions in human NEU1 - segments 139-159 (TM1) and 316-333 (TM2) - as potential transmembrane (TM) domains. In membrane mimicking environments, the corresponding peptides form stable α-helices and TM2 is suited for self-association. This was confirmed with full-size NEU1 by co-immunoprecipitations from membrane preparations and split-ubiquitin yeast two hybrids. The TM2 region was shown to be critical for dimerization since introduction of point mutations within TM2 leads to disruption of NEU1 dimerization and decrease of sialidase activity in membrane. In conclusion, these results bring new insights in the molecular organization of membrane-bound NEU1 and demonstrate, for the first time, the presence of two potential TM domains that may anchor NEU1 in the membrane, control its dimerization and sialidase activity.

Light activation of the LOV protein vivid generates a rapidly exchanging dimer.

Science.gov (United States)

Zoltowski, Brian D; Crane, Brian R

2008-07-08

The fungal photoreceptor Vivid (VVD) plays an important role in the adaptation of blue-light responses in Neurospora crassa. VVD, an FAD-binding LOV (light, oxygen, voltage) protein, couples light-induced cysteinyl adduct formation at the flavin ring to conformational changes in the N-terminal cap (Ncap) of the VVD PAS domain. Size-exclusion chromatography (SEC), equilibrium ultracentrifugation, and static and dynamic light scattering show that these conformational changes generate a rapidly exchanging VVD dimer, with an expanded hydrodynamic radius. A three-residue N-terminal beta-turn that assumes two different conformations in a crystal structure of a VVD C71V variant is essential for light-state dimerization. Residue substitutions at a critical hinge between the Ncap and PAS core can inhibit or enhance dimerization, whereas a Tyr to Trp substitution at the Ncap-PAS interface stabilizes the light-state dimer. Cross-linking through engineered disulfides indicates that the light-state dimer differs considerably from the dark-state dimer found in VVD crystal structures. These results verify the role of Ncap conformational changes in gating the photic response of N. crassa and indicate that LOV-LOV homo- or heterodimerization may be a mechanism for regulating light-activated gene expression.

Characterization of non-dimer DNA lesions and cellular damages caused by ultraviolet light

International Nuclear Information System (INIS)

Nakao, Kumi

1989-01-01

To understand the mechanisms of carcinogenicity and cytotoxicity induced by ultraviolet (UV) light, non-dimer DNA damages produced by near UV light (wave-length: 290∼320 nm) were examined by alkaline elution using Chinese hamster V-79 cells. UV exposure produced a dose-dependent induction of DNA single strand breaks and DNA-protein crosslinks. However, neither of these DNA lesions were repaired within a 24 hr incubation of the cells following UV exposure. Rather the number of these lesions increased. Also, UV exposure inhibited DNA and RNA synthesis. In addition, UV induced both cytotoxicity and chromosomal aberration. Electron spin resornance (ESR) studies showed that the exposure of cells to UV light resulted in the appearance of an ESR signal at -120degC. The roles of glutathione, vitamin E and vitamin B 2 , which were celluar antioxidant, on the induction of cytotoxicity by UV exposure were also examined. Pretreatment with vitamin E reduced the cytotoxicty caused by UV, whereas neither preteatment with vitamin B 2 nor the alteration of cellular gluthaione content affected the cytotoxicity. These results suggest that non-dimer DNA damages, such as DNA single strand breaks and DNA-protein crosslinks play an important role in inducing UV-carcinogenicity and UV-cytotoxicity, and that the mechanisms of these damages may be associated with the generation of free radicals. (author)

Smoking Discriminately Changes the Serum Active and Non-Active Forms of Vitamin B12

Directory of Open Access Journals (Sweden)

Niloofar Shekoohi

2017-08-01

Full Text Available Smoking may modify the appetite, and consequently affect nutrient intake and serum micronutrients. The effect of smoking on vitamin B12 status has been considered in several studies. The research proposed that organic nitrites, nitro oxide, cyanides, and isocyanides of cigarette smoke interfere with vitamin B12 metabolism, and convert it to inactive forms. This research was carried out to determine the serum level of active and inactive forms of vitamin B12 in male smokers in comparison with male nonsmokers. This is a case-control study, in which the participants were 85 male smokers and 85 male nonsmokers. The serum levels of total and active form of vitamin B12 were measured. Dietary intake was recorded by a quantitative food frequency questionnaire and one-day 24-hour dietary recall method. Independent two sample T test was used to compare quantitative variables between the case and control groups. The serum level of total vitamin B12 was not significantly different between two groups, but serum level of active form of vitamin B12 in the smoking group was significantly lower than non-smoking group (P<0.001. This is one of the first studies that evaluated the serum level of active form of vitamin B12 in smokers in the Iranian community. The results of this study identified that serum level of total vitamin B12 might be not different between smoking and non-smoking people, but the function of this vitamin is disturbed in the body of smokers through the reduction of serum level of active form of vitamin B12.

Preparation of 177Lu-DOTA/DTPA-Bz-Cys-RGD dimer and biodistribution evaluation in normal mice

International Nuclear Information System (INIS)

Sheng Feng; Jia Bing; Wang Fan; He Weiwei; Liu Zhaofei; Zhao Huiyun

2008-01-01

177 Lu-DOTA-Bz-Cys-RGD dimer and 177 Lu-DTPA-Bz-Cys-RGD dimer were prepared, and the in vitro and in vivo properties were compared. TLC and HPLC show that the labeling yields of two radiolabeled compounds are more than 95% under optimal conditions (pH=5.0, reacting at 100 degree C for 15-20 min), and the two radiolabeled compounds show pretty good in vitro stability. HPLC analyses and lg P values reveal that lipophilicity of 177 Lu-DOTA-Bz-Cys- RGD dimer is higher than 177 Lu-DTPA-Bz-Cys-RGD dimer. The uptake of 177 Lu-DTPA-Bz-Cys- RGD dimer in other tissues is significantly higher than that of 177 Lu-DOTA-Bz-Cys-RGD dimer at 4 h postinjection, except for blood and spleen. The in vivo stability of 177 Lu-DOTA-Bz-Cys-RGD dimer is much better than 177 Lu-DTPA-Bz-Cys-RGD dimer. Bz-DOTA is an ideal bifunctional chelator for 177 Lu labeling of RGD dimer. (authors)

Calculation of vibrational spectra for dioxouranium monochloride monomer and dimers

Science.gov (United States)

Umreiko, D. S.; Shundalau, M. B.; Zazhogin, A. P.; Komyak, A. I.

2010-09-01

Structural models were built and spectral characteristics were calculated based on ab initio calculations for the monomer and dimers of dioxouranium monochoride UO2Cl. The calculations were carried out in the effective core potential LANL2DZ approximation for the uranium atom and all-electron basis sets using DFT methods for oxygen and chlorine atoms (B3LYP/cc-pVDZ). The monomer UO2Cl was found to possess an equilibrium planar (close to T-shaped) configuration with C2v symmetry. The obtained spectral characteristics were analyzed and compared with experimental data. The adequacy of the proposed models and the qualitative agreement between calculation and experiment were demonstrated.

The Val{sup 192}Leu mutation in the {alpha}-subunit of {beta}-hexosaminidase A is not associated with the B1-variant form of Tay-Sachs disease

Energy Technology Data Exchange (ETDEWEB)

Hou, Y.; Vavougios, G.; Hinek, A. [Univ. of Toronto (Canada)] [and others

1996-07-01

Substitution mutations adversely affecting the {alpha}-subunit of {beta}-hexosaminidase A ({alpha}{beta}) (EC 3.2.1.52) result in Tay-Sachs disease. The majority affect the initial folding of the pro-{alpha} chain in the endoplasmic reticulum, resulting in its retention and degradation. A much less common occurrence is a mutation that specifically affects an {open_quotes}active-site{close_quotes} residue necessary for substrate binding and/or catalysis. In this case, hexosaminidase A is present in the lysosome, but it lacks all {alpha}-specific activity. This biochemical phenotype is referred to as the {open_quotes}B1-variant form{close_quotes} of Tay-Sachs disease. Kinetic analysis of suspected B1-variant mutations is complex because hexosaminidase A is heterodimeric and both subunits possess similar active sites. In this report, we examine a previously identified B1-variant mutation, {alpha}-Val{sup 192}Leu. Chinese hamster ovary cells were permanently cotransfected with an {alpha}-cDNA-construct encoding the substitution and a mutant {beta}-cDNA ({beta}-Arg{sup 211}Lys), encoding a {beta}-subunit that is inactive but normal in all other respects. We were surprised to find that the Val{sup 192}Leu substitution produced a pro-{alpha} chain that did not form {alpha}-{beta} dimers and was not transported to the lysosome. Finally, we reexamined the hexosaminidase activity and protein levels in the fibroblasts from the original patient. These data were also not consistent with the biochemical phenotype of the B1 variant of Tay-Sachs disease previously reported to be present. Thus, we conclude that the Val{sup 192}Leu substitution does not specifically affect the {alpha}-active site. 23 refs., 4 figs., 2 tabs.

Novel form of miR-29b suppresses bleomycin-induced pulmonary fibrosis.

Directory of Open Access Journals (Sweden)

Yuko Yamada

Full Text Available MicroRNA 29b (miR-29b replacement therapy is effective for suppressing fibrosis in a mouse model. However, to develop clinical applications for miRNA mimics, the side effects of nucleic acid drugs have to be addressed. In this study, we focused on miRNA mimics in order to develop therapies for idiopathic pulmonary fibrosis. We developed a single-stranded RNA, termed "miR-29b Psh-match," that has a unique structure to avoid problems associated with the therapeutic uses of miRNAs. A comparison of miR-29b Psh-match and double-stranded one, termed "miR-29b mimic" indicated that the single-stranded form was significantly effective towards fibrosis according to both in vivo and in vitro experiments. This novel form of miR-29b may become the foundation for developing an effective therapeutic drug for pulmonary fibrosis.

In vitro and in vivo mapping of the Prunus necrotic ringspot virus coat protein C-terminal dimerization domain by bimolecular fluorescence complementation.

Science.gov (United States)

Aparicio, Frederic; Sánchez-Navarro, Jesús A; Pallás, Vicente

2006-06-01

Interactions between viral proteins are critical for virus viability. Bimolecular fluorescent complementation (BiFC) technique determines protein interactions in real-time under almost normal physiological conditions. The coat protein (CP) of Prunus necrotic ringspot virus is required for multiple functions in its replication cycle. In this study, the region involved in CP dimerization has been mapped by BiFC in both bacteria and plant tissue. Full-length and C-terminal deleted forms of the CP gene were fused in-frame to the N- and C-terminal fragments of the yellow fluorescent protein. The BiFC analysis showed that a domain located between residues 9 and 27 from the C-end plays a critical role in dimerization. The importance of this C-terminal region in dimer formation and the applicability of the BiFC technique to analyse viral protein interactions are discussed.

Gap solitons in a chain of split-ring resonator dimers

Energy Technology Data Exchange (ETDEWEB)

Cui, Wei-na, E-mail: cuiweinaa@163.com [Department of Applied Physics, Nanjing University of Science and Technology, Nanjing 210094 (China); Li, Hong-xia, E-mail: hxli@njust.edu.cn [Department of Applied Physics, Nanjing University of Science and Technology, Nanjing 210094 (China); Sun, Min [Department of Applied Physics, Nanjing University of Science and Technology, Nanjing 210094 (China); Bu, Ling-bing [Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters, Key Laboratory for Aerosol-Cloud-Precipitation of China Meteorological Administration, Key Laboratory of Meteorological Disaster of Ministry of Education, Nanjing University of Information Science and Technology, Nanjing 210044 (China)

2017-06-21

Dynamics of a chain of split-ring resonator dimers with Kerr nonlinear interaction are investigated. A dimer is built as a pair of coupled split-ring resonators with different size. It is shown that the gap solitons with frequency lying in the gap exist due to the interaction of the discreteness and nonlinearity. Such localized structures are studied in the phase plane and analytical and numerical expressions are also obtained. - Highlights: • The coupling of the two modes is studied in the chain of split-ring resonator dimers with Kerr nonlinear interaction. • The evolution of the localized structures is studied in the phase plane. • This system supports gap solitons with the frequencies lying in the gap.

Thermal entanglement in an orthogonal dimer-plaquette chain with alternating Ising–Heisenberg coupling

International Nuclear Information System (INIS)

Paulinelli, H G; De Souza, S M; Rojas, Onofre

2013-01-01

In this paper we explore the entanglement in an orthogonal dimer-plaquette Ising–Heisenberg chain, assembled between plaquette edges, also known as orthogonal dimer plaquettes. The quantum entanglement properties involving an infinite chain structure are quite important, not only because the mathematical calculation is cumbersome but also because real materials are well represented by infinite chains. Using the local gauge symmetry of this model, we are able to map onto a simple spin-1 like Ising and spin-1/2 Heisenberg dimer model with single effective ion anisotropy. Thereafter this model can be solved using the decoration transformation and transfer matrix approach. First, we discuss the phase diagram at zero temperature of this model, where we find five ground states, one ferromagnetic, one antiferromagnetic, one triplet–triplet disordered and one triplet–singlet disordered phase, beside a dimer ferromagnetic–antiferromagnetic phase. In addition, we discuss the thermodynamic properties such as entropy, where we display the residual entropy. Furthermore, using the nearest site correlation function it is possible also to analyze the pairwise thermal entanglement for both orthogonal dimers. Additionally, we discuss the threshold temperature of the entangled region as a function of Hamiltonian parameters. We find a quite interesting thin reentrance threshold temperature for one of the dimers, and we also discuss the differences and similarities for both dimers. (paper)

Physical basis behind achondroplasia, the most common form of human dwarfism.

Science.gov (United States)

He, Lijuan; Horton, William; Hristova, Kalina

2010-09-24

Fibroblast growth factor receptor 3 (FGFR3) is a receptor tyrosine kinase that plays an important role in long bone development. The G380R mutation in FGFR3 transmembrane domain is known as the genetic cause for achondroplasia, the most common form of human dwarfism. Despite many studies, there is no consensus about the exact mechanism underlying the pathology. To gain further understanding into the physical basis behind the disorder, here we measure the activation of wild-type and mutant FGFR3 in mammalian cells using Western blots, and we analyze the activation within the frame of a physical-chemical model describing dimerization, ligand binding, and phosphorylation probabilities within the dimers. The data analysis presented here suggests that the mutation does not increase FGFR3 dimerization, as proposed previously. Instead, FGFR3 activity in achondroplasia is increased due to increased probability for phosphorylation of the unliganded mutant dimers. This finding has implications for the design of targeted molecular treatments for achondroplasia.

Theoretical Insights into a CO Dimerization Mechanism in CO2 Electroreduction.

Science.gov (United States)

Montoya, Joseph H; Shi, Chuan; Chan, Karen; Nørskov, Jens K

2015-06-04

In this work, we present DFT simulations that demonstrate the ability of Cu to catalyze CO dimerization in CO2 and CO electroreduction. We describe a previously unreported CO dimer configuration that is uniquely stabilized by a charged water layer on both Cu(111) and Cu(100). Without this charged water layer at the metal surface, the formation of the CO dimer is prohibitively endergonic. Our calculations also demonstrate that dimerization should have a lower activation barrier on Cu(100) than Cu(111), which, along with a more exergonic adsorption energy and a corresponding higher coverage of *CO, is consistent with experimental observations that Cu(100) has a high activity for C-C coupling at low overpotentials. We also demonstrate that this effect is present with cations other than H(+), a finding that is consistent with the experimentally observed pH independence of C2 formation on Cu.

In vitro aggregation behavior of a non-amyloidogenic λ light chain dimer deriving from U266 multiple myeloma cells.

Directory of Open Access Journals (Sweden)

Paolo Arosio

Full Text Available Excessive production of monoclonal light chains due to multiple myeloma can induce aggregation-related disorders, such as light chain amyloidosis (AL and light chain deposition diseases (LCDD. In this work, we produce a non-amyloidogenic IgE λ light chain dimer from human mammalian cells U266, which originated from a patient suffering from multiple myeloma, and we investigate the effect of several physicochemical parameters on the in vitro stability of this protein. The dimer is stable in physiological conditions and aggregation is observed only when strong denaturating conditions are applied (acidic pH with salt at large concentration or heating at melting temperature T(m at pH 7.4. The produced aggregates are spherical, amorphous oligomers. Despite the larger β-sheet content of such oligomers with respect to the native state, they do not bind Congo Red or ThT. The impossibility to obtain fibrils from the light chain dimer suggests that the occurrence of amyloidosis in patients requires the presence of the light chain fragment in the monomer form, while dimer can form only amorphous oligomers or amorphous deposits. No aggregation is observed after denaturant addition at pH 7.4 or at pH 2.0 with low salt concentration, indicating that not a generic unfolding but specific conformational changes are necessary to trigger aggregation. A specific anion effect in increasing the aggregation rate at pH 2.0 is observed according to the following order: SO(4(-≫Cl(->H(2PO(4(-, confirming the peculiar role of sulfate in promoting protein aggregation. It is found that, at least for the investigated case, the mechanism of the sulfate effect is related to protein secondary structure changes induced by anion binding.

Smoking Discriminately Changes the Serum Active and Non-Active Forms of Vitamin B12.

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Shekoohi, Niloofar; Javanbakht, Mohammad Hassan; Sohrabi, Marjan; Zarei, Mahnaz; Mohammadi, Hamed; Djalali, Mahmoud

2017-06-01

Smoking may modify the appetite, and consequently affect nutrient intake and serum micronutrients. The effect of smoking on vitamin B12 status has been considered in several studies. The research proposed that organic nitrites, nitro oxide, cyanides, and isocyanides of cigarette smoke interfere with vitamin B12 metabolism, and convert it to inactive forms. This research was carried out to determine the serum level of active and inactive forms of vitamin B12 in male smokers in comparison with male nonsmokers. This is a case-control study, in which the participants were 85 male smokers and 85 male nonsmokers. The serum levels of total and active form of vitamin B12 were measured. Dietary intake was recorded by a quantitative food frequency questionnaire and one-day 24-hour dietary recall method. Independent two sample T test was used to compare quantitative variables between the case and control groups. The serum level of total vitamin B12 was not significantly different between two groups, but serum level of active form of vitamin B12 in the smoking group was significantly lower than non-smoking group (Psmokers in the Iranian community. The results of this study identified that serum level of total vitamin B12 might be not different between smoking and non-smoking people, but the function of this vitamin is disturbed in the body of smokers through the reduction of serum level of active form of vitamin B12.

Imaging of deep venous thrombosis in patients using a radiolabelled anti-D-dimer Fab' fragment (99mTc-DI-DD3B6/22-80B3): results of a phase I trial

International Nuclear Information System (INIS)

Macfarlane, David; Socrates, Angelides; Larcos, George; Eisenberg, Paul; Roach, Paul; Gerometta, Michael; Smart, Richard; Tsui, Wendy; Scott, Andrew M.

2009-01-01

99m Tc-DI-DD3B6/22-80B3 (ThromboView registered, hereafter abbreviated to 99m Tc-DI-80B3 Fab') is a radiolabelled humanised monoclonal Fab' fragment with affinity and specificity for D-dimer domains of cross-linked fibrin. Detection of thromboembolic events has been demonstrated in canine models. The study objectives were evaluation of safety and characterisation of biodistribution, immunogenicity and pharmacokinetic profile of increasing doses of 99m Tc-DI-80B3 Fab' in subjects with acute lower-limb DVT. Twenty-six patients with acute lower limb DVT were enrolled. Of these, 21 received a single intravenous dose of 0.5 mg (n = 6), 1.0 mg (n = 9) or 2 mg (n = 6) 99m Tc-DI-80B3 Fab'. Blood and urine samples and gamma camera images were collected to 24 h after administration for pharmacokinetic and dosimetry analysis. Vital signs, electrocardiography, hematological and biochemical data and human anti-human antibody (HAHA) levels were monitored for up to 30 days following administration. Patients were assigned to either planar or single photon emission computed tomographic (SPECT) imaging of the thorax at 4 h following injection. Thirty-five adverse events were reported in 15 of the 21 subjects. Those deemed possibly related to administration of 99m Tc-DI-80B3 Fab' included mild hypertension, mild elevation of LD (lactate dehydrogenase) and moderate elevation of ALT (alanine transaminase). HAHA assays remained negative. Pharmacokinetics and organ dosimetry were comparable to prior normal volunteer data. Localisation of Thromboview registered to sites of known thrombus was evident as early as 30 min post-injection. In subjects with acute DVT, 99m Tc-DI-80B3 Fab' was well tolerated with favourable characteristics for the detection of acute venous thrombosis. (orig.)

Imaging of deep venous thrombosis in patients using a radiolabelled anti-D-dimer Fab' fragment (99mTc-DI-DD3B6/22-80B3): results of a phase I trial.

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Macfarlane, David; Socrates, Angelides; Eisenberg, Paul; Larcos, George; Roach, Paul; Gerometta, Michael; Smart, Richard; Tsui, Wendy; Scott, Andrew M

2009-02-01

(99m)Tc-DI-DD3B6/22-80B3 (ThromboView, hereafter abbreviated to (99m)Tc-DI-80B3 Fab') is a radiolabelled humanised monoclonal Fab' fragment with affinity and specificity for D-dimer domains of cross-linked fibrin. Detection of thromboembolic events has been demonstrated in canine models. The study objectives were evaluation of safety and characterisation of biodistribution, immunogenicity and pharmacokinetic profile of increasing doses of (99m)Tc-DI-80B3 Fab' in subjects with acute lower-limb DVT. Twenty-six patients with acute lower limb DVT were enrolled. Of these, 21 received a single intravenous dose of 0.5 mg (n = 6), 1.0 mg (n = 9) or 2 mg (n = 6) (99m)Tc-DI-80B3 Fab'. Blood and urine samples and gamma camera images were collected to 24 h after administration for pharmacokinetic and dosimetry analysis. Vital signs, electrocardiography, hematological and biochemical data and human anti-human antibody (HAHA) levels were monitored for up to 30 days following administration. Patients were assigned to either planar or single photon emission computed tomographic (SPECT) imaging of the thorax at 4 h following injection. Thirty-five adverse events were reported in 15 of the 21 subjects. Those deemed possibly related to administration of (99m)Tc-DI-80B3 Fab' included mild hypertension, mild elevation of LD (lactate dehydrogenase) and moderate elevation of ALT (alanine transaminase). HAHA assays remained negative. Pharmacokinetics and organ dosimetry were comparable to prior normal volunteer data. Localisation of Thromboview to sites of known thrombus was evident as early as 30 min post-injection. In subjects with acute DVT, (99m)Tc-DI-80B3 Fab' was well tolerated with favourable characteristics for the detection of acute venous thrombosis.

Breaking symmetry in the structure determination of (large) symmetric protein dimers

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Gaponenko, Vadim; Altieri, Amanda S.; Li, Jess; Byrd, R. Andrew [National Cancer Institute, Structural Biophysics Laboratory (United States)], E-mail: rabyrd@ncifcrf.gov

2002-10-15

We demonstrate a novel methodology to disrupt the symmetry in the NMR spectra of homodimers. A paramagnetic probe is introduced sub-stoichiometrically to create an asymmetric system with the paramagnetic probe residing on only one monomer within the dimer. This creates sufficient magnetic anisotropy for resolution of symmetry-related overlapped resonances and, consequently, detection of pseudocontact shifts and residual dipolar couplings specific to each monomeric component. These pseudocontact shifts can be readily incorporated into existing structure refinement calculations and enable determination of monomer orientation within the dimeric protein. This methodology can be widely used for solution structure determination of symmetric dimers.

Substrate-Induced Dimerization of Engineered Monomeric Variants of Triosephosphate Isomerase from Trichomonas vaginalis.

Directory of Open Access Journals (Sweden)

Samuel Lara-Gonzalez

Full Text Available The dimeric nature of triosephosphate isomerases (TIMs is maintained by an extensive surface area interface of more than 1600 Å2. TIMs from Trichomonas vaginalis (TvTIM are held in their dimeric state by two mechanisms: a ball and socket interaction of residue 45 of one subunit that fits into the hydrophobic pocket of the complementary subunit and by swapping of loop 3 between subunits. TvTIMs differ from other TIMs in their unfolding energetics. In TvTIMs the energy necessary to unfold a monomer is greater than the energy necessary to dissociate the dimer. Herein we found that the character of residue I45 controls the dimer-monomer equilibrium in TvTIMs. Unfolding experiments employing monomeric and dimeric mutants led us to conclude that dimeric TvTIMs unfold following a four state model denaturation process whereas monomeric TvTIMs follow a three state model. In contrast to other monomeric TIMs, monomeric variants of TvTIM1 are stable and unexpectedly one of them (I45A is only 29-fold less active than wild-type TvTIM1. The high enzymatic activity of monomeric TvTIMs contrast with the marginal catalytic activity of diverse monomeric TIMs variants. The stability of the monomeric variants of TvTIM1 and the use of cross-linking and analytical ultracentrifugation experiments permit us to understand the differences between the catalytic activities of TvTIMs and other marginally active monomeric TIMs. As TvTIMs do not unfold upon dimer dissociation, herein we found that the high enzymatic activity of monomeric TvTIM variants is explained by the formation of catalytic dimeric competent species assisted by substrate binding.

Sensitive determination of dopamine levels via surface-enhanced Raman scattering of Ag nanoparticle dimers.

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Yu, Xiantong; He, XiaoXiao; Yang, Taiqun; Zhao, Litao; Chen, Qichen; Zhang, Sanjun; Chen, Jinquan; Xu, Jianhua

2018-01-01

Dopamine (DA) is an important neurotransmitter in the hypothalamus and pituitary gland, which can produce a direct influence on mammals' emotions in midbrain. Additionally, the level of DA is highly related with some important neurologic diseases such as schizophrenia, Parkinson, and Huntington's diseases, etc. In light of the important roles that DA plays in the disease modulation, it is of considerable significance to develop a sensitive and reproducible approach for monitoring DA. The objective of this study was to develop an efficient approach to quantitatively monitor the level of DA using Ag nanoparticle (NP) dimers and enhanced Raman spectroscopy. Ag NP dimers were synthesized for the sensitive detection of DA via surface-enhanced Raman scattering (SERS). Citrate was used as both the capping agent of NPs and sensing agent to DA, which is self-assembled on the surface of Ag NP dimers by reacting with the surface carboxyl group to form a stable amide bond. To improve accuracy and precision, the multiplicative effects model for surface-enhanced Raman spectroscopy was utilized to analyze the SERS assays. A low limits of detection (LOD) of 20 pM and a wide linear response range from 30 pM to 300 nM were obtained for DA quantitative detection. The SERS enhancement factor was theoretically valued at approximately 10 7 by discrete dipole approximation. DA was self-assembled on the citrate capped surface of Ag NPs dimers through the amide bond. The adsorption energy was estimated to be 256 KJ/mol using the Langmuir isotherm model. The density functional theory was used to simulate the spectral characteristics of SERS during the adsorption of DA on the surface of the Ag dimers. Furthermore, to improve the accuracy and precision of quantitative analysis of SERS assays with a multiplicative effects model for surface-enhanced Raman spectroscopy. A LOD of 20 pM DA-level was obtained, and the linear response ranged from 30 pM to 300 nM for quantitative DA detection. The

Capturing the Role of Explicit Solvent in the Dimerization of RuV (bda) Water Oxidation Catalysts.

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Zhan, Shaoqi; Mårtensson, Daniel; Purg, Miha; Kamerlin, Shina C L; Ahlquist, Mårten S G

2017-06-06

A ground-breaking empirical valence bond study for a soluble transition-metal complex is presented. The full reaction of catalyst monomers approaching and reacting in the Ru V oxidation state were studied. Analysis of the solvation shell in the reactant and along the reaction coordinate revealed that the oxo itself is hydrophobic, which adds a significant driving force to form the dimer. The effect of the solvent on the reaction between the prereactive dimer and the product was small. The solvent seems to lower the barrier for the isoquinoline (isoq) complex while it is increased for pyridines. By comparing the reaction in the gas phase and solution, the proposed π-stacking interaction of the isoq ligands is found to be entirely driven by the water medium. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of strategies to control Fab light chain dimer during mammalian expression and purification: A universal one-step process for purification of correctly assembled Fab.

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Spooner, Jennifer; Keen, Jenny; Nayyar, Kalpana; Birkett, Neil; Bond, Nicholas; Bannister, David; Tigue, Natalie; Higazi, Daniel; Kemp, Benjamin; Vaughan, Tristan; Kippen, Alistair; Buchanan, Andrew

2015-07-01

Fabs are an important class of antibody fragment as both research reagents and therapeutic agents. There are a plethora of methods described for their recombinant expression and purification. However, these do not address the issue of excessive light chain production that forms light chain dimers nor do they describe a universal purification strategy. Light chain dimer impurities and the absence of a universal Fab purification strategy present persistent challenges for biotechnology applications using Fabs, particularly around the need for bespoke purification strategies. This study describes methods to address light chain dimer formation during Fab expression and identifies a novel CH 1 affinity resin as a simple and efficient one-step purification for correctly assembled Fab. © 2015 Wiley Periodicals, Inc.

Single chain Fc-dimer-human growth hormone fusion protein for improved drug delivery.

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Zhou, Li; Wang, Hsuan-Yao; Tong, Shanshan; Okamoto, Curtis T; Shen, Wei-Chiang; Zaro, Jennica L

2017-02-01

Fc fusion protein technology has been successfully used to generate long-acting forms of several protein therapeutics. In this study, a novel Fc-based drug carrier, single chain Fc-dimer (sc(Fc) 2 ), was designed to contain two Fc domains recombinantly linked via a flexible linker. Since the Fc dimeric structure is maintained through the flexible linker, the hinge region was omitted to further stabilize it against proteolysis and reduce FcγR-related effector functions. The resultant sc(Fc) 2 candidate preserved the neonatal Fc receptor (FcRn) binding. sc(Fc) 2 -mediated delivery was then evaluated using a therapeutic protein with a short plasma half-life, human growth hormone (hGH), as the protein drug cargo. This novel carrier protein showed a prolonged in vivo half-life and increased hGH-mediated bioactivity compared to the traditional Fc-based drug carrier. sc(Fc) 2 technology has the potential to greatly advance and expand the use of Fc-technology for improving the pharmacokinetics and bioactivity of protein therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alkane dimers interaction