Academic literature on the topic 'Domaine Gla'
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Journal articles on the topic "Domaine Gla"
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Davis-Harrison, Rebecca L., Narjes Tavoosi, Mary Clay, John M. Boettcher, Chad M. Rienstra, and James H. Morrissey. "Structural Insights Into How Clotting Proteins with GLA Domains Bind to Membrane Surfaces." Blood 116, no. 21 (November 19, 2010): 1141. http://dx.doi.org/10.1182/blood.v116.21.1141.1141.
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Abstract Abstract 1141 Most steps in the blood coagulation cascade obligatorily take place on membrane surfaces and are dependent on the exposure of phosphatidylserine (PS). Many coagulation proteins bind to PS-containing membrane bilayers in a calcium-dependent manner via gamma-carboxyglutamate-rich (GLA) domains. In spite of their importance, a clear picture of how GLA domains bind to the membrane interface has yet to emerge. A further intriguing aspect of the membrane's role in blood coagulation is that certain phospholipids, most notably phosphatidylethanolamine (PE), strongly synergize with PS to promote clotting reactions. The mechanisms of this synergy, and of PE's contribution to GLA domain binding, are poorly understood – although a number of hypotheses have been put forward. We now propose a new hypothesis to explain GLA domain binding to membranes, which we term the ABC (Anything But Choline) hypothesis; it invokes two main types of protein-phospholipid interactions: a single L-serine-specific binding site in each GLA domain; and multiple “phosphate-specific” interactions in which the phosphate groups of non-phosphatidylcholine phospholipids form coordination complexes with the tightly bound calcium ions in GLA domains. We have utilized liposomes and nanoscale phospholipid bilayers (Nanodiscs) in studies employing a series of techniques including solid-state NMR (SSNMR) and surface plasmon resonance (SPR) to address the mechanism of GLA domain-membrane interactions. We provide direct evidence in favor of the ABC hypothesis for GLA domain binding to membrane surfaces. Using SSNMR, we demonstrate that two distinct PS headgroup conformations are induced by binding of calcium ions, and that a third, novel PS headgroup conformation is induced when the prothrombin GLA domain engages the membrane. SPR studies have allowed for the determination of thermodynamic profiles of GLA domains interacting with phospholipid bilayers containing PS and/or PE, providing further insights to the mechanisms of GLA domain-membrane interactions. Disclosures: No relevant conflicts of interest to declare.
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Majumder, Rinku, Judson Craft, Alireza Rezaie, R. Barry, and Dougald Monroe. "Role of Gamma-Carboxyglutamic Acid (GLA) Domain in Phosphatidylserine (PS)-Regulated Activity of Factor IXa." Blood 110, no. 11 (November 16, 2007): 2696. http://dx.doi.org/10.1182/blood.v110.11.2696.2696.
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Abstract Both factors Xa and IXa are vitamin-K-dependent serine proteases that consist of disulfide-linked heavy and light chains. The heavy chain contains the serine protease active site, while the light chain contains the GLA (gamma-carboxyglutamic acid) domain, EGF-I (epidermal growth factor-like region) and EGF-II domains. Effect of PS on FXa: We have extensively studied the interaction of factor Xa with 1, 2-dicaproyl-sn-glycero-3-phospho-L-serine (C6PS). C6PS is a soluble analogue of phosphatidylserine, which is present in platelet membranes; it serves as a model for the effect of membrane-bound PS on factor Xa activity and structure. We located three C6PS binding sites to different domains of factor Xa using a combination of activity, circular dichroism, fluorescence, and equilibrium dialysis measurements, showing that : the Gla domain binds C6PS only in the absence of calcium (kd ∼ 1 mM); a calcium-dependent, regulatory, PS-binding site exists in the EGFN domain when linked by calcium to the Gla domain; and a second calcium-requiring site exists in the EGFC-catalytic domains and shares residues with the substrate recognition site. We have shown that full functional response to C6PS requires linkage of the Gla, EGFNC, and catalytic domains in the presence of calcium. Recently we have observed that the proteolytic activity of des EGFN factor Xa is not affected in the presence of C6PS, locating more precisely a significant component of the PS-triggered regulatory site to the EGFN domain. Efect of PS on FIXa: We have previously reported that C6PS induces a calcium-dependent conformational change in factor IXa that regulates the amidolytic and proteolytic activities. We have also shown that factor IXa binds 2 molecules of C6PS. Here we have examined the role of the GLA domain in this C6PS regulation of factor IXa using a GLA-domainless variant of factor IXa (GD-IXa). In the absence of the GLA domain, binding to C6PS has no effect on the rate of proteolytic or amidolytic activity of GD-IXa toward both factor X and synthetic substrates. The binding of C6PS to GD-IXa studied using intrinsic tryptophan fluorescence (Kd = ∼50μM) was different from that for native factor IXa (Kd = ∼2μM). The critical micelle concentration (CMC) of C6PS under the conditions of these experiments (∼300μM) was much greater than the C6PS concentrations used in our experiments. We conclude that: C6PS does bind to GD-IXa, but at a reduced affinity compared to factor IXa; C6PS does not regulate the amidolytic or proteolytic activities of factor IXa in the absence of GLA domain. This could be due to two C6PS sites existing in FIXa, with the regulatory site requiring the Gla domain (as observed for FXa), or to a requirement for the Gla domain for the regulatory activity of a single site. Future studies looking at the stoichiometry of binding of C6PS with GD-IXa will help distinguish between these possibilities. Supported by Supported by NHLBI (HL 072827).
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Geng, Jie-Ping, and Francis J. Castellino. "The Propeptides of Human Protein C, Factor VII, and Factor IX Are Exchangeable with Regard to Directing Gamma-Carboxylation of these Proteins." Thrombosis and Haemostasis 76, no. 02 (1996): 205–7. http://dx.doi.org/10.1055/s-0038-1650555.
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SummaryThe specificity of the propeptide sequence in directing vitamin Independent post-translational γ-carboxylation has been assessed by examination of the extent of processing of chimeric constructs of blood coagulation factor VII (fVII), factor IX (fIX) and protein C (PC). One chimera consisted of a protein in which the γ-carboxyglutamic acid (Gla)/helical stack domain of PC (amino acid residues 1 to 46) was replaced by that of fIX (residues 1 to 47) in an otherwise intact PC. Another consisted of the same construction of a fVII/PC Gla domain-based mutant protein. The final chimera contained the leader/propeptide sequence of PC (residues -42 to -1) replaced by that of fIX (residues -46 to -1). In each case, all Glu-precursor Gla residues in the Gla domains of the proteins were fully processed to Gla. These results demonstrate that the propeptides of fIX and PC are capable of directing γ-carboxylation of the Gla regions of either protein, that the propeptide of PC can fully function in γ-carboxylation of the Gla region of fVII, and further suggest that, with regard to γ-carboxylation, communications between the propeptides and Gla domains in intact proteins are general in nature.
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Allan, J. A., A. J. P. Docherty, P. J. Barker, N. S. Huskisson, J. J. Reynolds, and G. Murphy. "Binding of gelatinases A and B to type-I collagen and other matrix components." Biochemical Journal 309, no. 1 (July 1, 1995): 299–306. http://dx.doi.org/10.1042/bj3090299.
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Matrix sequestration of matrix metalloproteinases may be important for the facilitation of remodelling events and the migration of cells through the extracellular matrix. Using an ELISA technique we studied the ability of pro and active forms of gelatinases A and B (GLA and GLB) to bind to matrix components and the contribution made by the different enzyme domains. Pro and active forms of GLA and GLB bound to type-I and type-IV collagens, gelatin and laminin films. Binding to collagens occurred exclusively via the N-terminal portion of the molecule in both of the gelatinases; deletion of the fibronectin-like domain in GLA abolished binding. Fibronectin was shown to compete with GLA, confirming that binding occurs through this domain. GLA and GLB competed for binding to collagen type I, whereas collagenase and stromelysin bound to different sites and could be co-localized with the gelatinases. We conclude that gelatinases have different binding specificities from those previously documented for stromelysin and collagenase, which bind through their C-terminal domains to collagen fibrils.
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Gopinath, Subash C. B., Yasuo Shikamoto, Hiroshi Mizuno, and Penmetcha K. R. Kumar. "Snake-venom-derived Factor IX-binding protein specifically blocks the γ-carboxyglutamic acid-rich-domain-mediated membrane binding of human Factors IX and X." Biochemical Journal 405, no. 2 (June 27, 2007): 351–57. http://dx.doi.org/10.1042/bj20061737.
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A potent anticoagulant protein, IX-bp (Factor IX binding protein), has been isolated from the venom of Trimeresurus flavoviridis (habu snake) and is known to bind specifically to the Gla (γ-carboxyglutamic acid-rich) domain of Factor IX. To evaluate the molecular basis for its anticoagulation activity, we assessed its interactions with various clotting factors. We found that the anticoagulation activity is primarily due to binding to the Gla domains of Factors IX and X, thus preventing these factors from recognizing phosphatidylserine on the plasma membrane. The present study suggests that ligands that bind to the Gla domains of Factors IX and X may have the potential to become novel anticoagulants.
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Szymanski, D. B., R. A. Jilk, S. M. Pollock, and M. D. Marks. "Control of GL2 expression in Arabidopsis leaves and trichomes." Development 125, no. 7 (April 1, 1998): 1161–71. http://dx.doi.org/10.1242/dev.125.7.1161.
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More than twenty genes are required for the correct initiation, spacing, and morphogenesis of trichomes in Arabidopsis. The initial selection of trichome precursors requires the activity of both the GLABROUS1 (GL1) and TRANSPARENT TESTA GLABROUS (TTG) genes. The GLABRA2 (GL2) gene is required for subsequent phases of trichome morphogenesis such as cell expansion, branching, and maturation of the trichome cell wall. Previous studies have shown that GL2 is a member of the homeodomain class of transcription factors. Here we report a detailed analysis of GL2 expression in the shoot using anti-GL2 antibodies and the GUS reporter gene fused to the GL2 promoter. The GL2 expression profile in the shoot is complex, and involves spatial and temporal variation in developing leaves and trichomes. Two separate promoter domains that are expressed in trichomes were identified. GL2, like GL1, is expressed in developing trichomes and in cells surrounding trichomes during early stages of trichome development. Unlike GL1, GL2 expression persists in mature trichomes. It was found that while GL1 and TTG were not required for the initiation of GL2 expression in the non-trichome cells, the presence of a functional GL1 or TTG gene was able to increase GL2 expression in these cells compared to ttg gl1 plants. The hypothesis that GL1 regulates aspects of GL2 expression is consistent with epistatic analysis of gl1 and gl2 and the expression patterns of GL1 and GL2. In support of this hypothesis, it was found that ectopic expression of GL1 in the presence of ectopic expression of the maize R gene, which can bypass the requirement for TTG, can ectopically activate GL2 transcription.
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Im, U., and M. Kanakidou. "Impacts of East Mediterranean megacity emissions on air quality." Atmospheric Chemistry and Physics 12, no. 14 (July 23, 2012): 6335–55. http://dx.doi.org/10.5194/acp-12-6335-2012.
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Abstract. Megacities are large urban agglomerations with intensive anthropogenic emissions that have significant impacts on local and regional air quality. In the present mesoscale modeling study, the impacts of anthropogenic emissions from the Greater Istanbul Area (GIA) and the Greater Athens Area (GAA) on the air quality in GIA, GAA and the entire East Mediterranean are quantified for typical wintertime (December 2008) and summertime (July 2008) conditions. They are compared to those of the regional anthropogenic and biogenic emissions that are also calculated. Finally, the efficiency of potential country-based emissions mitigation in improving air quality is investigated. The results show that relative contributions from both cities to surface ozone (O3) and aerosol levels in the cities' extended areas are generally higher in winter than in summer. Anthropogenic emissions from GIA depress surface O3 in the GIA by ~ 60% in winter and ~ 20% in summer while those from GAA reduce the surface O3 in the GAA by 30% in winter and by 8% in summer. GIA and GAA anthropogenic emissions contribute to the fine particulate matter (PM2.5) levels inside the cities themselves by up to 75% in winter and by 50% (GIA) and ~ 40% (GAA), in summer. GIA anthropogenic emissions have larger impacts on the domain-mean surface O3 (up to 1%) and PM2.5 (4%) levels compared to GAA anthropogenic emissions (<1% for O3 and ≤2% for PM2.5) in both seasons. Impacts of regional anthropogenic emissions on the domain-mean surface pollutant levels (up to 17% for summertime O3 and 52% for wintertime fine particulate matter, PM2.5) are much higher than those from Istanbul and Athens together (~ 1% for O3 and ~ 6% for PM2.5, respectively). Regional biogenic emissions are found to limit the production of secondary inorganic aerosol species in summer up to 13% (non-sea-salt sulfate (nss-SO42−) in rural Athens) due to their impact on oxidant levels while they have negligible impact in winter. Finally, the responses to country-based anthropogenic emission mitigation scenarios inside the studied region show increases in O3 mixing ratios in the urban areas of GIA and GAA, higher in winter (~ 13% for GIA and 2% for GAA) than in summer (~ 7% for GIA and <1% for GAA). On the opposite PM2.5 concentrations decrease by up to 30% in GIA and by 20% in GAA with the highest improvements computed for winter. The emission reduction strategy also leads to domain-wide decreases in most primary pollutants like carbon monoxide (CO) or nitrogen oxides (NOx) for both seasons. The results show the importance of long range transport of pollutants for the air quality in the East Mediterranean. Thus, improvements of air quality in the East Mediterranean require coordinated efforts inside the region and beyond.
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Sun, Yong-Hui, Lei Shen, and Björn Dahlbäck. "Gla domain–mutated human protein C exhibiting enhanced anticoagulant activity and increased phospholipid binding." Blood 101, no. 6 (March 15, 2003): 2277–84. http://dx.doi.org/10.1182/blood-2002-06-1691.
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Protein C is a member of the vitamin K– dependent protein family. Proteins in this family have similar γ-carboxyglutamic acid (Gla)–rich domains, but their affinities for negatively charged phospholipid membranes vary more than 1000-fold. We have shown that it is possible to enhance anticoagulant activity and membrane affinity of protein C by selective mutagenesis of the Gla domain. In this study, 3 new mutants, Q10G11N12 (QGN), S23E32D33Y44 (SEDY), and Q10G11N12S23E32D33Y44 (QGNSEDY), were created. In plasma-based coagulation assays, the activated form of QGNSEDY (QGNSEDY-APC) demonstrated approximately 20-fold higher anticoagulant activity than wild-type activated protein C (WT APC), while QGN-APC and SEDY-APC did not. Both normal activated factor V (FVa) and FVa Leiden (Arg506Gln) were degraded much more efficiently by QGNSEDY-APC than by WT APC in the presence as well as in the absence of protein S. Binding of protein C variants to negatively charged phospholipid membranes was investigated using light scattering and the BIAcore technique. QGNSEDY demonstrated 3- to 7-fold enhanced binding as compared with WT protein C, suggesting the membrane affinity to be influenced by several residues located at different parts of the Gla domain. The anticoagulant activity as well as phospholipid binding ability was only enhanced when multiple regions of the Gla domain were modified. The results provide insights into the molecular mechanisms that are involved in determining the binding affinity of the interaction between Gla domains and phospholipid membranes. The unique properties of QGNSEDY-APC suggest this APC variant possibly to have greater therapeutic potential than WT APC.
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Chen, Shu-wen, Jean-François Schved, Jean-Luc Pellequer, and Muriel Giansily-Blaizot. "Model of a Ternary Complex between Activated Factor VII, Tissue Factor and Factor IX." Thrombosis and Haemostasis 88, no. 07 (2002): 74–82. http://dx.doi.org/10.1055/s-0037-1613157.
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SummaryUpon binding to tissue factor, FVIIa triggers coagulation by activating vitamin K-dependent zymogens, factor IX (FIX) and factor X (FX). To understand recognition mechanisms in the initiation step of the coagulation cascade, we present a three-dimensional model of the ternary complex between FVIIa:TF:FIX. This model was built using a full-space search algorithm in combination with computational graphics. With the known crystallographic complex FVIIa:TF kept fixed, the FIX docking was performed first with FIX Gla-EGF1 domains, followed by the FIX protease/EGF2 domains. Because the FIXa crystal structure lacks electron density for the Gla domain, we constructed a chimeric FIX molecule that contains the Gla-EGF1 domains of FVIIa and the EGF2-protease domains of FIXa. The FVIIa:TF:FIX complex has been extensively challenged against experimental data including site-directed mutagenesis, inhibitory peptide data, haemophilia B database mutations, inhibitor antibodies and a novel exosite binding inhibitor peptide. This FVIIa:TF:FIX complex provides a powerful tool to study the regulation of FVIIa production and presents new avenues for developing therapeutic inhibitory compounds of FVIIa:TF:substrate complex.
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Davis-Harrison, Rebecca L., Narjes Tavoosi, Vincent S. Pureza, and James H. Morrissey. "Phospholipid Synergy in Prothrombinase Activity." Blood 118, no. 21 (November 18, 2011): 1175. http://dx.doi.org/10.1182/blood.v118.21.1175.1175.
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Abstract Abstract 1175 Most steps in the blood coagulation cascade obligatorily take place on membrane surfaces and are dependent on the exposure of phosphatidylserine (PS). Previous studies from our lab and others have shown that phosphatidylethanolamine (PE) poorly supports clotting reactions by itself, but strongly synergizes with PS to promote several membrane-dependent steps in the blood clotting cascade, although the mechanism for PE-PS synergy has been unclear. We recently put forward a new mechanistic explanation – which we termed the ABC or Anything But Choline hypothesis – for how PS and PE synergize to enhance factor X (fX) activation by the factor VIIa-tissue factor complex (Tavoosi et al., J. Biol. Chem. 286:23247–53, 2011). The membrane contribution to this reaction is dominated by the affinity of fX for the membrane surface; since fX binds to membranes via its gamma-carboxyglutamate-rich (GLA) domain, the ABC hypothesis therefore focuses on the mechanisms by which GLA domains engage the phospholipid bilayer. We identified two main types of GLA domain-phospholipid interactions: a single phospho-L-serine-specific binding site in each GLA domain; and multiple ”phosphate-specific” interactions in which the phosphate groups of non-phosphatidylcholine phospholipids form coordination complexes with the tightly bound calcium ions in GLA domains. In the current study, we test the ABC hypothesis in the context of the prothrombinase complex – i.e., activation of prothrombin by the membrane-bound complex of fXa and factor Va (fVa). Using a variety of approaches including surface plasmon resonance analyses, we measured the contributions of varying phospholipid compositions to the membrane binding affinities of fXa, fVa and prothrombin, as well as to the enzymatic activity of prothrombinase. Our results suggest that phospholipid synergy in prothrombinase activity differs in certain respects from that observed for the factor VIIa-tissue factor complex. Not only did PS synergize with PE for enhancing the activity of prothrombinase, but phosphatidylglycerol (PG) and phosphatidylacid (PA) also synergized with PE, albeit more weakly than with PS (i.e., significantly higher levels of PG or PA in the presence of PE were required to achieve prothrombinase activities comparable to mixtures of PS and PE). In contrast, PE failed to synergize with either PG or PA to support fX activation by the factor VIIa-tissue factor complex. These differences primarily arise from differential membrane binding of the substrates for these two complexes (fX for factor VIIa-tissue factor and prothrombin for prothrombinase). The data suggest that the phospho-L-serine-specific binding site in the GLA domain of prothrombin may not be as stringent as that of fX, as high levels of PG or PA can substitute for PS in membrane binding of prothrombin but not for fX. This study provides further insights into the membrane's role in regulating blood clotting reactions, specifically the binding interactions between GLA domains and membrane surfaces. Disclosures: No relevant conflicts of interest to declare.
Dissertations / Theses on the topic "Domaine Gla"
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Marlu, Raphaël. "Conception rationnelle de nouvelles protéines thérapeutiques dans l'hémophilie : variants du facteur Xa dépourvus du domaine Gla." Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-00949107.
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Introduction : L'hémophilie est une maladie génétique de la coagulation due à un déficit en facteur VIII ou en facteur IX. Ces déficits sont responsables d'un déficit du complexe ténase intrinsèque (VIIIa-IXa). De plus, le complexe ténase extrinsèque (facteur tissulaire - VIIa) est physiologiquement rapidement inhibé par le TFPI lié au facteur Xa. Nous avons évalué la capacité d'une forme tronquée du facteur Xa (GDXa), dépourvue de domaine Gla à se lier au TFPI et à soulager l'inhibition physiologique du complexe ténase extrinsèque. Matériel et Méthodes : Dans une première partie, nous avons évalué la capacité du GDXa à restaurer la génération de thrombine de plasmas d'hémophiles A et B sévères sans et avec inhibiteurs. Nous avons également comparé les profils de génération de thrombine obtenus après addition du GDXa à ceux obtenus en présence d'anticorps neutralisants anti-TFPI ou anti-antithrombine. Enfin, nous avons comparé les cinétiques enzymatiques de neutralisation du facteur Xa et du GDXa par le TFPI et l'antithrombine. Dans une seconde partie, nous avons étudié in silico les interactions entre la chaîne lourde du facteur Xa et le TFPI pour détecter les zones d'interaction défavorables. Cette étude a identifié des acides aminés du facteur Xa qui pourraient être substitués pour optimiser l'interaction avec le TFPI. Les résultats in silico ont orienté nos choix de mutagenèse dirigée pour concevoir différents variants moléculaires du GDXa (R138F, R138G, R138I) où l'arginine 138 est substituée. Ces variants protéiques ont été produits de façon recombinante dans des cellules HEK293E. La capacité des différents variants à restaurer la génération de thrombine de plasmas d'hémophiles a été testée avec les surnageants de culture cellulaires correspondants. Résultats : Dans la première partie, nous avons montré que le GDXa est capable de restaurer la génération de thrombine de plasmas d'hémophiles A et B sans et avec inhibiteurs. Comparativement au facteur Xa, le GDXa montre une affinité moindre pour le TFPI tandis que les affinités du GDXa et du facteur Xa pour l'antithrombine sont identiques. Enfin, malgré une demi-vie courte, l'effet du GDXa sur la génération de thrombine est maintenu pendant au moins une heure. Dans la seconde partie, nous avons produit les différents variants R138F, R138G et R138I en cellules HEK293E et montré que les surnageants de culture cellulaire étaient capables de restaurer la génération de thrombine de plasmas d'hémophiles de façon plus efficace que le GDXa. Conclusion : Comme le GDXa est capable de restaurer la génération de thrombine de plasmas d'hémophiles, nos résultats suggèrent que le GDXa pourrait être une alternative efficace aux thérapeutiques hémostatiques court-circuitantes actuelles chez les hémophiles sans ou avec inhibiteurs. Les résultats obtenus renforcent l'hypothèse que l'activité pro-coagulante du GDXa serait liée à la formation d'un complexe GDXa-TFPI limitant la formation du complexe Xa-TFPI nécessaire à l'inhibition physiologique du complexe ténase extrinsèque. De plus, notre approche rationnelle basée sur une étude in silico visant à augmenter l'affinité du TFPI pour le GDXa a permis de produire différents variants moléculaires du GDXa dont l'activité procoagulante in vitro est augmentée par rapport au GDXa.
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Saller, François. "Etude fonctionnelle de l'extrémité amino-terminale de la protéine S." Paris 5, 2004. http://www.theses.fr/2004PA05P633.
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Au cours de cette thèse, nous avons montré dans un premier travail que le domaine riche résidus acides γ-carboxyglutamiques en Gla de la protéine S (PS) ne lui permet pas seulement de se lier aux phospholipides mais qu'il intervient également dans une interaction directe avec la protéine C activée (PCa). De plus, nous avons identifié deux faces opposées du domaine Gla de la PS, l'une participant à l'interaction avec les phospholipides et l'autre à l'interaction avec la PCa. Ces résultats nouveaux suggèrent qu'il existe une zone de contact entre le domaine Gla de la PS et celui de la PCa. De plus, la conformation du domaine Gla de la PS est fortement influencée par une boucle adjacente, la boucle sensible à la thrombine (TSR). En effet, nous avons montré que la TSR est indispensable pour la liaison de la PS aux membranes et que cette boucle influence de façon non spécifique la conformation Ca2+-dépendante du domaine Gla en jouant un rôle d'espaceur entre le domaine Gla et le domaine EGF1 de la PS. Alors que les effets de mutations au sein de la TSR sont généralement faibles sur l'expression de l'activité cofacteur de la PS, nous avons enfin démontré dans cette étude un rôle direct fort de cette TSR dans l'interaction avec la PCaWe have first shown that the protein S (PS) domain rich in ?-carboxyglutamic acids (Gla domain) not only mediates phospholipid binding but is also involved in direct interactions with activated protein C (APC). Furthermore, we have identified two opposite faces of the PS Gla domain, the one participating in interaction with phospholipids and the other involved in interaction with APC. These results are novel and suggest that a contact may exist between the PS Gla domain and the APC Gla domain. Moreover, the conformation of the PS Gla domain is strongly affected by a tethered disulfide loop, the thrombin-sensitive region (TSR). Indeed, we have shown that the TSR is required for PS binding to phospholipid membranes and that the latter loop non specifically modulates the Ca2+-dependent conformation of the PS Gla domain by playing a spacer role between the Gla and EGF1 domains of PS. Although the effects of mutations within the TSR are generally weak on the expression of PS APC cofactor activity, we have eventually demonstrated a strong direct role of the TSR in interaction with APC
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Thieba, Camilia Annik. "The Role of GLP Domains in Spreading of the G9a/GLP Complex and Regulation of the β-globin Gene Expression." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/22830.
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Marked by a defect in the production of the Beta (β)-globin chain that make-up hemoglobin, Beta (β)-thalassemia is the most prevalent form of inherited single-gene disorders in the world. To understand the molecular mechanisms that govern the expression of the β-globin polypeptide encoded by the β-globin locus, we examined closely the enzymes involved in the epigenetic regulation of gene expression through histone 3 lysine 9 mono and di-methylation (H3K9 me1/2). G9a-like protein (GLP), a mammalian methyltransferase involved in the establishment and maintenance of H3K9 me1/2 mark at euchromatin, regions was found to be critical for the full activation of the adult β-globin genes in vivo during Murine erythroleukemia cell line (MEL) differentiation. Though it was initially hypothesized that GLP binding to H3K9 me1/2 mark through its Ankyrin domain was key to its activating function, we found that Flag- GLP ankyrin mutants E817R and W791A unable to bind to the methyl mark, are able to activate β-globin genes as well as their wild-type counterpart. Additionally, this study found that the embryonic gene εγ, known to be re-activated after G9a KD at the mRNA level, was effectively transcribed at the protein level using Triton Urea Acetic acid (TAU) western blots, thereby identifying potential therapeutic applications for treatment for β-thalassemia patients.
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Preston, Roger James Stephen. "The protein C Gla domain : structure-function relationships." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416058.
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Yevstafiev, Dmytro. "Deciphering the Mechanism of G9a Spreading Genome-wide." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/32005.
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The cell differentiation process is associated with activation and repression of different genes, whereby the formation of heterochromatin is mediated by spreading of repressor proteins along large chromatin domains. Some of these proteins are methyltransferases, including GLP and G9a that are implicated in the addition of mono- and dimethyl groups to lysine 9 at Histone 3. Despite extensive research the exact mechanism of binding and spreading of G9a and GLP is unclear. To better understand the molecular mechanisms through which G9a and GLP bind to chromatin we tested the in vivo binding of a mutant G9a that is unable to bind to H3K9me2 histone marks via its Ankyrin domain. Murine erythroleukemia (MEL) cell line with expression of mutant G9a was generated using recombinant DNA technologies; G9a binding targets genome-wide were detected by the analysis of ChIP-sequencing data. We validated ChIP-sequencing data providing a reliable tool to visualize G9a targets in MEL cells. We also found that G9a Ankyrin mutant bound to all tested regions suggesting that the Ankyrin domain is not the only factor that contributes to the binding of G9a on chromatin in vivo.
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Chen, Taiping 1963. "Biochemical and functional characterization of the GSG (GRP33, Sam68, GLD-1) domain." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36561.
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The GSG (G&barbelow;RP33, S&barbelow;am68, G&barbelow;LD-1) domain is a tripartite protein module of ∼200 amino acids. It consists of an hnRNP K homology (KH) domain and two flanking regions N- and C-terminal to the KH domain Called the NK region and CK region, respectively. The KH domain embedded in the GSG domain has longer loops 1 and 4 compared to other KH domains. The physiological significance of the GSG domain is demonstrated by the fact that genetic mutations in the GSG domain result in developmental defects in various species. The primary goal of this thesis is to characterize the biochemical properties and functions of the GSG domain. We demonstrated that the GSG domain proteins Sam68, Qk1, GRP33, and GLD-1 are RNA-binding proteins that self-associate into multimers. Sam68 complexes bound homopolymeric RNA and the SH3 domains of p59fyn and phospholipase Cgamma1 in vitro, indicating that Sam68 associates with RNA and signaling molecules as a multimer. The formation of Sam68 complex was inhibited by p59fyn, suggesting that Sam68 oligomerization is regulated by tyrosine phosphorylation. Deletion studies in Sam68 and Qk1 demonstrated that the GSG domain is required for both self-association and RNA binding. Sam68 oligomerization requires the extended loops 1 and 4 of the KH domain and the Qk1 dimerization domain is mapped to the NK region. A Qk1 lethal point mutation, altering glutamic acid 48 to a glycine in the NK region, abolishes Qk1 self-association but has no effect on its ability to bind total cellular RNA. The mutant Qk1 protein is more potent than wild-type Qk1 in inducing apoptosis when expressed in NIH 3T3 cells, suggesting that failure to dimerize may be the molecular mechanism for the embryonic lethality. In addition to mediating self-association and RNA binding, the Sam68 GSG domain plays a role in protein localization. We demonstrated by indirect immunofluorescence studies that Sam68 is concentrated in novel nuclear structures, termed Sam
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Chen, Taiping. "Biochemical and functional characterization of the GSG (GRP33, Sam68, GLD-1) domain." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0031/NQ64532.pdf.
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Vallabh, Sushmitha. "Targeted Epigenetic Suppression of Th2 Cytokines Expression." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1505131225205869.
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Sanz, Lionel. "Role des modifications des histones dans le maintien et la lecture de l’empreinte génomique chez la souris." Thesis, Montpellier 2, 2010. http://www.theses.fr/2010MON20107.
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L'empreinte génomique est un mécanisme épigénétique qui conduit à l'expression d'un seul des deux allèles parentaux pour une centaine de gènes autosomaux chez les mammifères. La majorité des gènes soumis à l'empreinte est regroupée en clusters et tous ces gènes sont sous le contrôle de séquences discrètes appelées ICR (Imprinting Control Region). Les ICRs sont marquées épigénétiquement par une méthylation d'ADN et des modifications des histones alléliques. La méthylation d'ADN au niveau de ces ICRs est un facteur clé de l'empreinte et va être établie dans les lignées germinales suivant le sexe de l'embryon. Après fécondation, le nouvel embryon portera les empreintes paternelles et maternelles, ces empreintes devront alors être maintenues pendant tout le développement et interprétés dans le but de conduire à l'expression allélique des gènes soumis à l'empreinte. Cependant, la méthylation d'ADN ne peut expliquer à elle seule tous les aspects de l'empreinte génomique. Ainsi, d'autres marques épigénétiques doivent agir dans le maintien et la lecture de ces empreintes. Nous avons mis en évidence dans un premier temps que le contrôle de l'expression allélique dans le cerveau de Grb10 repose sur la résolution d'un domaine bivalent allélique spécifiquement dans le cerveau. Ces résultats mettent en avant pour la première fois un domaine bivalent dans le contrôle de l'expression des gènes soumis à l'empreinte et propose un nouveau mécanisme dans l'expression tissu spécifique de ces gènes. D'autre part, bien que des études en cellules ES aient démontré un rôle de G9a dans le maintien des empreintes au cours du développement embryonnaire, nos données suggèrent que G9a ne serait pas essentielle a ce maintien dans un contexte in vivoGenomic imprinting is a developmental mechanism which leads to parent-of-origin-specific expression for about one hundred genes in mammals. Most of imprinted genes are clustered and all are under control of sequence of few kilobases called Imprinting Control Region or ICR. ICRs are epigenetically marked by allelic DNA methylation and histone modifications. DNA methylation on ICRs is a key factor which is established in germ cells according to the sex of the embryo. After fecundation, the new embryo will harbored both paternal and maternal imprints which have to be maintained during the development and read to lead to allelic expression of imprinted genes. However, allelic DNA methylation alone cannot explain every aspect of genomic imprinting. Thus, there should be other epigenetic marks which act in the maintaining and reading of the imprints.Our data first indicate that bivalent chromatin, in combination with neuronal factors, controls the paternal expression of Grb10 in brain, the bivalent domain being resolved upon neural commitment, during the developmental window in which paternal expression is activated. This finding highlights a novel mechanism to control tissue-specific imprinting. On an other hand, although previous studies in ES cells show a role for G9a in the maintaining of imprints during embryonic development, our data suggest that G9a would not be essential in an in vivo model
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Herschkorn, Nathalie. "Etude des propriétés optiques des structures à puits quantiques multiples GaAs-GaA/As dans le domaine de l'infrarouge moyen liées aux transitions intrabande." Grenoble 2 : ANRT, 1988. http://catalogue.bnf.fr/ark:/12148/cb376142859.
Full textBooks on the topic "Domaine Gla"
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Carvalho, Max de. Enquete sur les domaines mouvants: Avec les estamps originaux de Kazimir Glaz. Toronto: Toronto Center for Contemporary Art, 2005.
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Vietnam. Văn bản hướng dã̂n thực hiện đè̂n bù thiệt hại khi nhà nước thu hò̂i đá̂t đẻ̂ sử dụng vào mục đích quó̂c phòng, an ninh, lợi ích quó̂c gia, lợi ích công cộng. Hà Nội: Nhà xuá̂t bản Xây dựng, 1999.
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Thu nhập, đời sống, việc làm của người có đất bị thu hồi để xây dựng các khu công nghiệp, khu đô thị kết cấu hạ tầng kinh tế- xã hội các công trình công cộng phục vụ lợi ích quốc gia. Hà Nội: Nhà xuá̂t bản Chính trị quốc gia, 2007.
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Caproni, Giorgio. Il mondo ha bisogno dei poeti. Edited by Melissa Rota. Florence: Firenze University Press, 2014. http://dx.doi.org/10.36253/978-88-6655-677-0.
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Intrigante e apparentemente facile, l’intervista può a volte essere generatrice di stress. In ogni caso è quello che pensava Caproni, che però era anche convinto che solo nel rapporto con il lettore la poesia potesse trovare il “suo reale valore” e la sua possibilità di esistenza. Per questo, piegandosi con garbo e ritrosia alle domande, accettò negli anni di guidare i suoi interlocutori nel mondo misterioso e inafferrabile dell’arte, là dove si producono idee e emozioni con la sola “musica delle parole”. Per aiutarci ad afferrarla, quella imprendibile musica, in questo libro struggente ed ironico, ci parla delle dimore vitali (Genova, Livorno), delle figure lariche, delle passioni giovanili, delle ferite immedicate (Olga, la guerra), del bisogno di scrivere, tradurre, conoscere, e della proustiana introiezione del passato sulla “carta velina della memoria”. Per oltre centoquaranta volte (tanti sono i pezzi ricostruiti e riuniti adesso per la prima volta grazie al prezioso e accurato lavoro di ricerca di Melissa Rota) le interviste restituiscono – come sottolinea Anna Dolfi nella bella introduzione – al di fuori di ogni retorica e gigantografia, le grain de la voix , le grain de la vie di un intellettuale ‘eretico’, libero nelle scelte e nella determinazione del proprio destino. Sì che una sottile malia ci guida nel seguire su queste pagine troppo a lungo dimenticate i segni di una vocazione, e il ‘tremore’ che, stroncando una carriera, lasciò gli scatti nervosi del violinista all’inconfondibile piglio dei versi a venire.
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Dolfi, Anna, ed. Notturni e musica nella poesia moderna. Florence: Firenze University Press, 2019. http://dx.doi.org/10.36253/978-88-6453-803-7.
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Che cos’è la notte? Come definirla e segnarne i limiti? È più o è meno mobile lo sguardo di chi la fissa; persiste nella notte la funzione cornice? In che modo la difficoltà di vedere favorisce l’invenzione artistica, l’interrogazione sull’infinito e la morte, i quesiti sull’immaginario, il sogno, il ricordo, l’oblio? Da domande come queste è partita Anna Dolfi nell’ideare un libro di grande novità e suggestione che, tra notturni e musica, si chiede come la letteratura, la pittura, il cinema, l’opera lirica, le tradizioni popolari, le canzoni, abbiano parlato di cecità e di visione, di ossessione e paura, di notti «tenere», disperate, sublimi, misteriose, mistiche, di notti di ‘malattia’, di notti riparatrici, di notti bianche e di notti insonni, quando il tentativo è resistere creando, per sfidare l’approssimarsi dell’alba. L’icona della mozartiana Regina della notte, assieme a quella di un Pierrot schönberghiano, ha accompagnato come in controluce una cinquantina di studiosi e giovani ricercatori italiani e stranieri che, partendo dal Settecento, dai canti di Ossian, lungo un percorso notturno europeo sostenuto da teorici (Nietzsche, Bachelard, Jankélévitch…) e musica (Mozart, Chopin, Schubert, Schumann, Fauré, Debussy, Britten…), hanno lavorato su Novalis, Hölderlin, il Romanticismo tedesco, Rilke, Celan, Müller, Hugo, Chenier, Baudelaire, Proust, Cocteau, Bonnefoy…, declinando i notturni italiani dalle elegie cimiteriali di Pindemonte a Leopardi, Di Giacomo, D’Annunzio, Onofri, Campana, Saba, Ungaretti, Sbarbaro, Montale, Penna, Pavese, Gatto, Caproni, Luzi, Bigongiari, Fortini, Jacobbi, Ripellino, Pasolini, Giudici, Rosselli, Sanguineti, De Signoribus, la Anedda, Magrelli… Aperto da testi inediti portoghesi di Ruggero Jacobbi, da versi e traduzioni di De Signoribus e di Vegliante, il volume, dalla notte di Donizetti arriva a quella dei cantautori (De Gregori, Dalla…), spingendosi al limite di notturni elettrici che rivelano in poesia gli squarci urbani di una tormentata società tra fi ne secolo e inizio millennio.
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Enquete Sur Les Domaines Mouvants: Avec Les Estamps Originaux de Kazimir Glaz. Not Avail, 2005.
Find full textBook chapters on the topic "Domaine Gla"
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Altieri, Amanda S., Michael E. Perlman, Kathleen C. Pugh, Robert E. London, Richard G. Hiskey, and Lee G. Pedersen. "Structural properties of a Gla-domain peptide of prothrombin fragment I." In Peptides, 285–86. Dordrecht: Springer Netherlands, 1992. http://dx.doi.org/10.1007/978-94-011-2264-1_102.
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Baleja, James D., Steven J. Freedman, Barbara C. Furie, and Bruce Furie. "NMR structures for the membrane binding gla domain of blood coagulation factor IX." In Techniques in Protein Chemistry, 131–38. Elsevier, 1996. http://dx.doi.org/10.1016/s1080-8914(96)80017-2.
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Becker, Richard C., and Frederick A. Spencer. "Historical Perspectives in Hemostasis, Coagulation, and Fibrinolysis: A Foundation for Understanding Thrombotic Disorders and Developing Effective Treatment." In Fibrinolytic and Antithrombotic Therapy. Oxford University Press, 2006. http://dx.doi.org/10.1093/oso/9780195155648.003.0005.
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Hemostasis, the prompt cessation of bleeding at a site of vascular injury, is among the most fundamental physiologic and teleologically vital defense mechanisms in nature. Without a functionally intact hemostatic mechanism, death could ensue rapidly even after minor traumas associated with everyday life. In mammalian blood coagulation, regulated by a complex network of integrated biochemical events, five protease factors (f ) (fIIa [thrombin], fVIIa, fIXa, fXa, and protein C) interact with five cofactors (tissue factor, f VIIIa, fVa, thrombomodulin, and protein S) to regulate the generation of fibrin (Davidson et al., 2003). Although each component of the mammalian coagulation network has unique functional properties, available data based on gene organizations, protein structure, and sequence analysis suggest that it may have resulted from the reduplication and diversification of two gene structures over 400 million years ago. A vitamin K–dependent serine protease is composed of a γ-carboxylated glutamic acid (GLA) epidermal growth factor-like (EGF) 1–EGF 2-serine protease domain structure common to fVII, fIX, fX, and protein C, and the A1-A2-B-AB-C1-C2 domain structure common to fV and fVIII. Prothrombin is also a vitamin K–dependent serine protease; however, it contains kringle domains rather than EGF domains (suggesting a replacement during gene duplication and shuffling). Analyses of active site function amino acid residues reveal distinguishing characteristics of thrombin from other serine proteases, supporting its position as the ancestral blood enzyme (Krem and Cera, 2002; McLysaght et al., 2002). The rapid transformation of fluid blood to a gel-like substance (clot) has been a topic of great interest to scientists, physicians, and philosophers since the days of Plato and Aristotle ( Jewett, 1892; Lee, 1952). However, it was not until the beginning of the 18th century that blood clotting (coagulation) was appreciated as a means to stem blood loss from wounds (hemostasis) (Petit, 1731). As with other areas of science, the microscope played a pivotal role in the understanding of coagulation. In the mid-17th century, Marcello Malpighi separated the individual components of a blood clot into fibers, cells, and serum (Forester, 1956).
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Brezany, Peter, Ivan Janciak, and A. Min Tjoa. "Ontology-Based Construction of Grid Data Mining Workflows." In Data Warehousing and Mining, 913–41. IGI Global, 2008. http://dx.doi.org/10.4018/978-1-59904-951-9.ch054.
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This chapter introduces an ontology-based framework for automated construction of complex interactive data mining workflows as a means of improving productivity of Grid-enabled data exploration systems. The authors first characterize existing manual and automated workflow composition approaches and then present their solution called GridMiner Assistant (GMA), which addresses the whole life cycle of the knowledge discovery process. GMA is specified in the OWL language and is being developed around a novel data mining ontology, which is based on concepts of industry standards like the Predictive Model Markup Language, Cross Industry Standard Process for Data Mining and Java Data Mining API. The ontology introduces basic data mining concepts like data mining elements, tasks, services, etc. In addition, conceptual and implementation architectures of the framework are presented and its application to an example taken from the medical domain is illustrated. The authors hope that the further research and development of this framework can lead to productivity improvements, which can have significant impact on many real-life spheres. For example, it can be a crucial factor in achievement of scientific discoveries, optimal treatment of patients, productive decision making, cutting costs, etc.
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Feliciati, Pierluigi. "Improving the impact of digital cultural heritage : system, content and users’ challenges." In Patrimoine et Humanités numériques, 3–16. Editions des archives contemporaines, 2020. http://dx.doi.org/10.17184/eac.3588.
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Dans le domaine de la culture, l’impact du patrimoine numérique sur la société est stratégique et constitue la qualité intrinsèque des ressources elles-mêmes. La tendance actuelle incite les institutions GLAM (acronyme anglais pour « Galleries, Libraries, Archives and Museums », en français « Galeries, Bibliothèques, Archives et Musées ») à dépasser la conception du patrimoine comme « Beau » valable en soi, accessible seulement à quelques spécialistes, et au contraire à favoriser des collisions proactives avec les besoins des communautés, leurs perceptions, leurs choix. Ainsi, étant donné que les éléments cruciaux pour un projet de patrimoine digital semblent être les contenus auxquels il donne accès, les fonctionnalités disponibles, et les usagers, il devient essentiel de tenir compte des besoins et attentes de ces derniers, qu’ils soient explicites ou non, pour assurer un service convenable.Cette contribution présente brièvement les principaux problèmes et les possibilités offertes par une structuration des études d’utilisateurs de produits culturels numériques, en se concentrant sur le système, les contenus et les utilisateurs, qui constituent les trois pôles de cette structure interactive.
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Sharma, Laxmikant, and Suman Sinha. "Measuring Dynamics of Ecological Footprint as an Index of Environmental Sustainability at the Regional Level Using Geospatial Information Technology." In Environmental Information Systems, 965–80. IGI Global, 2019. http://dx.doi.org/10.4018/978-1-5225-7033-2.ch042.
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Ecological Footprint (EF) analysis is the spatial measurement of ecological load exerted by the humans on the earth that arises from the concept of sustainability and sustainable use of Earth's resources. A region-based EF study is conducted for Birla Institute of Technology, Mesra (India) campus to improve its sustainability. Highlight of the study is the explicitness of the methodology for determining the EF that incorporates analysis derived from conversion factors mentioned in the Ecological Footprint consultancy publications along with inputs from GIS domain. Questionnaire-based survey from the respondents regarding resource utilization and geospatial enumeration of land use land cover that harbors the population and their resources are the two integral parts of the analysis. Total EF of the institution campus is calculated to be 0.645 gha/ individual. This analysis provides a strong framework for combining efforts in a manner that can communicate the immediate priorities for improving the sustainability strategy of the campus area.
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Bose, Goutam Kumar, and Pritam Pain. "Nature-Inspired Metaheuristic Approach for Multi-Objective Optimization During WEDM Process." In Soft Computing Techniques and Applications in Mechanical Engineering, 91–122. IGI Global, 2018. http://dx.doi.org/10.4018/978-1-5225-3035-0.ch004.
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In this research paper Wire-Electric Discharge Machining (WEDM) is applied to machine AISI-D3 material in order to measure the performance of multi-objective responses like high material removal rate and low roughness. This contradictory objective is accomplished by the control parameters like Pulse on Time (Ton), Pulse off Time (Toff), Wire Feed (W/Feed) and Wire Tension (W/Ten) employing brass wire. Here the orthogonal array is used to developed 625 parametric combinations. The optimization of the contradictory responses is carried out in a metaheuristic environment. Artificial Neural Network is employed to train and validate the experimental result. Primarily the individual responses are optimized by employing Firefly algorithm (FA). This is followed by a multi-objective optimization through Genetic algorithm (GA) approach. As the results obtained through GA infer a domain of solutions, therefore Grey Relation Analysis (GRA) is applied where the weights are considered through Fuzzy set theory to ascertain the best parametric combination amongst the set of feasible alternatives.
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Sharma, Laxmikant, and Suman Sinha. "Measuring Dynamics of Ecological Footprint as an Index of Environmental Sustainability at the Regional Level using Geospatial Information Technology." In Advances in Geospatial Technologies, 265–84. IGI Global, 2017. http://dx.doi.org/10.4018/978-1-5225-1814-3.ch014.
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Ecological Footprint (EF) analysis is the spatial measurement of ecological load exerted by the humans on the earth that arises from the concept of sustainability and sustainable use of Earth's resources. A region-based EF study is conducted for Birla Institute of Technology, Mesra (India) campus to improve its sustainability. Highlight of the study is the explicitness of the methodology for determining the EF that incorporates analysis derived from conversion factors mentioned in the Ecological Footprint consultancy publications along with inputs from GIS domain. Questionnaire-based survey from the respondents regarding resource utilization and geospatial enumeration of land use land cover that harbors the population and their resources are the two integral parts of the analysis. Total EF of the institution campus is calculated to be 0.645 gha/ individual. This analysis provides a strong framework for combining efforts in a manner that can communicate the immediate priorities for improving the sustainability strategy of the campus area.
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Cox, Morgan A., Aaron J. Cavosie, Michael Poelchau, Thomas Kenkmann, Phil A. Bland, and Katarina Miljković. "Shock deformation microstructures in xenotime from the Spider impact structure, Western Australia." In Large Meteorite Impacts and Planetary Evolution VI. Geological Society of America, 2021. http://dx.doi.org/10.1130/2021.2550(19).
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ABSTRACT The rare earth element–bearing phosphate xenotime (YPO4) is isostructural with zircon, and therefore it has been predicted that xenotime forms similar shock deformation microstructures. However, systematic characterization of the range of micro structures that form in xenotime has not been conducted previously. Here, we report a study of 25 xenotime grains from 10 shatter cones in silicified sandstone from the Spider impact structure in Western Australia. We used electron backscatter diffrac tion (EBSD) in order to characterize deformation and microstructures within xenotime. The studied grains preserve multiple sets of planar fractures, lamellar {112} deformation twins, high-angle planar deformation bands (PDBs), partially recrystallized domains, and pre-impact polycrystalline grains. Pressure estimates from micro structures in coexisting minerals (quartz and zircon) allow some broad empirical constraints on formation conditions of ~10–20 GPa to be placed on the observed microstructures in xenotime; at present, more precise formation conditions are unavailable due to the absence of experimental constraints. Results from this study indicate that the most promising microstructures in xenotime for recording shock deformation are lamellar {112} twins, polycrystalline grains, and high-angle PDBs. The {112} deformation twins in xenotime are likely to be a diagnostic shock indicator, but they may require a different stress regime than that of {112} twinning in zircon. Likewise, polycrystalline grains are suggestive of impact-induced thermal recrystallization; however, in contrast to zircon, the impact-generated polycrystalline xenotime grains here appear to have formed in the solid state, and, in some cases, they may be difficult to distinguish from diagenetic xenotime with broadly similar textures.
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Fields, Gregg B., and Janelle L. Lauer-Fields. "Principles and Practice of Solid-Phase Peptide Synthesis." In Synthetic Peptides. Oxford University Press, 2002. http://dx.doi.org/10.1093/oso/9780195132618.003.0006.
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Peptides play key structural and functional roles in biochemistry, pharmacology, and neurobiology, and are important probes for research in enzymology, immunology, and molecular biology. The amino acid building blocks can be among the 20 genetically encoded L-residues, or else unusual ones, and the sequences can be linear, cyclic, or branched. It follows that rapid, efficient, and reliable methodology for the chemical synthesis of these molecules is of utmost interest. A number of synthetic peptides are significant commercial or pharmaceutical products, ranging from the sweet dipeptide L-Asp-L-Phe-OMe (aspartame) to clinically used hormones such as oxytocin, adrenocorticotropic hormone, calcitonin, and gonadotropin releasing hormone (GnRH) super-agonists. Synthesis can lead to potent and selective new drugs by judicious substitutions that change functional groups and/or conformations of the parent peptide. These include introduction of N- or C-alkyl substituents, unnatural or D-amino acids, side-chain modifications including sulfate or phosphate groups or carbohydrate moieties, and constraints such as disulfide bridges between half-cystines or side-chain lactams between Lys and Asp or Glu. Commercially important products that evolved from such studies include protease inhibitors, such as captopril and other angiotensin converting enzyme (ACE) inhibitors, peptidomimetic HIV protease inhibitors, and the somatostatin analog lanreotide. Most of the biologically or medicinally important peptides which are the targets for useful structure-function studies by chemical synthesis comprise under 50 amino acid residues, but occasionally a synthetic approach can lead to important conclusions about small proteins (full or domains) in the 100-200 residue size range. Methods for synthesizing peptides are divided conveniently into two categories: solution (classical) and solid-phase pep tide synthesis (SPPS). The classical methods have evolved since the beginning of the twentieth century, and they are described amply in several reviews and books (Wünsch, 1974; Finn and Hofmann, 1976; Bodanszky and Bodanszky, 1984; Goodman et al, 2001). The solid-phase alternative was conceived and elaborated by R. B. Merrifield beginning in 1959, and has also been covered comprehensively (Erickson and Merrifield, 1976; Birr, 1978; Barany and Merrifield, 1979; Stewart and Young, 1984; Merrifield, 1986; Barany et al., 1987, 1988; Kent, 1988; Atherton and Sheppard, 1989; Fields and Noble, 1990; Barany and Albericio, 1991; Fields et al., 1992; Gutte, 1995; Fields, 1997; Lloyd-Williams et al., 1997; Chan and White, 2000; Kates and Albericio, 2000).
Conference papers on the topic "Domaine Gla"
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Pareti, F. I., K. Nliya, P. J. Kostel, J. M. McPherson, T. S. Zimmerman, and Z. M. Ruggeri. "IDENTIFICATION OF A SECOND COLLAGEN-BINDING DOMAIN IN HUMAN VON WILLEBRAND FACTOR." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642877.
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We have recently reported (Journal of Biological Chemistry 261: 15310-15315, 1986) that von Willebrand factor (vWF) possesses a collagen-binding domain localized in a reduced and alkylated tryptic fragment of apparent 52/48 kDa molecular weight extending between residues Val (449) and Lys (728) of the constituent subunit. This proteolytic fragment of vWF also contains a glycoprotein lb-binding domain and a heparin-binding domain. We have now identified a second collagen-binding domain in the Staphylococcus aureus V8 protease-generated fragment I that extends from residue Gly (911) to Glu (1365). The two binding domains exhibit different interaction with collagens of different origin. The reduced and alkylated 52/48 kDa tryptic fragment was a potent inhibitor of vWF binding to equine collagen type I, but had no effect on the binding to bovine collagen type I and III. In contrast, a purified fraction containing the unreduced 52/48 kDa domain inhibited vWF binding to all types of collagen, as did anti-52/48 kDa monoclonal antibodies. Some of these antibodies, however, were more effective in inhibiting binding to equine collagen. On the other hand, fragment I markedly inhibited the binding of vWF to bovine collagen type I and III, but was less effective with equine collagen type I. Direct binding studies using 425j_qabeled fragment I demonstrated that the association constant was 5 to 10 times greater with the bovine collagens than with the equine collagen. The Staphylococcus aureus V8 protease-generated fragment III, which extends from residue Ser (1) to Glu (1365) and contains both collagen-binding domains, was the most potent inhibitor of vWF binding to all types of collagen tested. Thus, vWF has at least two collagen-binding domains. Native conformation appears to be necessary for binding of the 52/48 kDa domain to bovine collagen type I and III, but not to the equine collagen type I tested. The two domains appear to function concurrently in mediating vWF binding to collagen.
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Jorgensen, M. J., MJ Rabiet, A. B. Cantor, B. Furie, C. L. Brown, C. B. Shoemaker, and B. C. Furie. "VITAMIN K-DEPENDENT γ-CARBOXYLATION OF FACTOR IX REQUIRES A RECOGNITION SITE CONTAINED WITHIN THE PROPEPTIDE." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643564.
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The vitamin K-dependent proteins, including Factor IX (FIX), are calcium-binding proteins that undergo vitamin K-dependent post-translational modification to convert amino terminal glutamic aoid residues to Gla residues. Sequence homology among the propeptides of these proteins suggests a role for this region in designating the adjacent glutamic acid-rich domain for γ-carboxylation during intraoellular processing. Mutations vere made in the propeptide (residues -1 to -18) of FIX, and the effects on γ-carboxylation were assessed. The human FIX cDNA coding sequenoe was modified using oligonucleotide-directed site-specific mutagenesis and was expressed in Chinese hamster ovary cells. The extent of γ-carboxylation of secreted FIX was determined by (1) ability to interact with conformation-specific antibodies directed against the Gla-dependent, metal-stabilized, native structure of FIX, and (2) direct Gla analysis of the alkaline hydrolysate. Using the unmodified coding sequence, 64 ± 17 % of recombinant Factor IX bound to the conformation-specific antibodies, and 9.4 ± 0.7 Gla residues were found (compared with 12 Gla in plasma FIX). When the 18-residue propeptide was deleted, secreted FIX contained no detectable native FIX antigen and no detectable Gla. Similarly, point mutations leading to substitution of Ala for Phe at residue -16 or Glu for Ala at residue -10 led to secretion of FIX containing 2% and 6% native antigen, respectively, and approximately 1-2 Gla residues. The molecular weight of each of the reoombinant FIX species, as estimated by SDS-PAGE, was identical to that of plasma FIX. NH2-terminal sequence analysis of the mutant FIX speoies yielded the NH2-terminal sequence of plasma FIX. These data indicate that the mutations made in the propeptide did not interfere with intracellular proteolytic prooessing of FIX. We conolude that the FIX propeptide participates in defining a recognition site that designates an adjacent glutamic acid-rich domain for γ-carboxylation. The association of the propeptide with the γ-carboxylation recognition site provides the first demonstration of a specific function served by a propeptide in post-translational protein processing.
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Ashok Kumar, A., Margaret Insley, Jay Gambee, Sharon J. Busby, and Kathleen L. Berkner. "SITE SPECIFIC MUTAGENESIS WITHIN THE GLA-DOMAIN OF HUMAN FACTOR IX." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644079.
Full textAbstract:
Factor IX, a plasma protein, plays a critical role in blood coagulation. The biological activity of factor IX as well as several other plasma proteins depends on the presence of gamma-carboxy glutamic acid (Gla) residues in their amino terminal region. In vitro mutagenesis has been used to selectively replace Gla residues of factor IX with aspartic acid (Asp) residues in order to establish the contribution of individual as well as paired Gla residues to the normal functioning of the protein. These substitutions were made at positions 7, 15, 20 and 26 in human factor IX. In addition, residue number 18, a cysteine has been changed to serine in an attempt to disrupt the highly conserved disulfide bond in the gla-domain. The gla-domain mutants will be produced in mammalian cells and compared with native recombinant factor IX. A rapid immunoaffinity purification procedure, which has been used to obtain recombinant factor IX produced in the presence or absence of vitamin K, is being used to purify the mutants. Protein sequence analysis has been used to confirm complete processing and proper gamma-carboxylation of recombinant factor IX. The properties of these mutants as compared to human factor IX will be discussed.
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KÖhlin, A., and J. Stenflo. "HIGH AFFINITY CALCIUM BINDING TO DOMAINES OF PROTEIN C THAT ARE HOMOLOGUS TO THE EPIDERMAL GROWTH FACTOR." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643645.
Full textAbstract:
In addition to γ-carboxyglutamic acid (Gla)-dependent calcium binding all of the vitamin K-dependent plasma proteins, except prothrombin, have one or two high affinity calcium binding sites that do not require the Gla residues. A common denominator among these proteins (factors IX, X, protein C, protein Z and protein S) is that they have domaines that are homologus to the epidermal growth factor (EGF) precursor. In factors VII,IX,X, protein C and in protein Z the aminoterminal of two EGF homology regions contain one residue of β-hydroxyaspartic acid (Hya) whereas in protein S the aminoterminal EGF homology region contains Hya and the three following contain one β-hydroxyasparagine residue each.In an attempt to elucidate the role of the EGF homology regions in the Gla independent calcium binding we have isolated a tryptic fragment (residue 44-138) from the light chain of human protein C. The fragment was isolated using a monoclonal antibody that recognizes a calcium ion stabilized epitope that is expressed both in intact protein C and in protein C lacking the Gla domaine.The antibody bound the isolated EGF homology region in the presence of calcium ions but not in EDTA containing buffer. A calcium ion titration showed half maximal binding at approximately 200 μM Ca2+. The metal ion induced conformational change in the isolated fragment was also studied with affinity purified rabbit antibodies against Gla domainless protein C. Antibodies that bound in the presence of calcium ions and that could be eluted with EDTA recognized the metal ion induced conformational change in the isolated EGF homology domain. Our results suggest that one or both of the EGF homology regions are involved in the Gla-independent high affinity calcium binding in the vitamin K-dependent plasma proteins.
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Sugo, T., S. Tanabe, K. Shinoda, and M. Matsuda. "MONOCLONAL ANTIBODIES THAT RECOGNIZE Ca2+-INDUCED CONFORMER OF PROTEIN C, INDEPENDENT OF GLA RESIDUES." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643644.
Full textAbstract:
Monoclonal antibodies (MCA’s) were prepared against human protein C (PC) according to Köhler & Milstein, and those that recognize the Ca2+-dependent PC conformers were screened by direct ELISA in the presence of 2 mM either CaCl2 or EDTA. Out of nine MCAߣs thus screened, five MCA's designated as HPC-1˜5, respectively, were found to react with PC in the presence of Ca2+ but not EDTA. By SDS-PAGE coupled with Western Blotting performed in the presence of 2 mM CaCl2, we found that two MCA’s HPC-1 and 2, recognized the light chain, and two others, HPC-3 and 4, recognized the heavy chain of PC. But another MCA, HPC-5 was found to react with only non-reduced antigens. Further study showed that HPC-1 and 5 failed to react with the Gla-domainless PC, i.e. PC from which the N-terminal Gla-domain of the light chain had been cleaved off by α-chymotrypsin. However, all the other three MCA's retained the reactivity with the antigen in the presence of Ca2+ even after the Gla-domain had been removed. The binding of these MCA’s to PC in the presence of Ca2+ was found to be saturable with respect to the Ca2+ concentration and the half maximal binding for each MCA was calculated to be about 0.5+mM. Moreover, many other divalent cations such as Mg2+, Mn2+ , Ba2+, Zn2+, Co2+, Sr2+, were found to substitute for Ca2+ in inducing the metal ion-dependent but Gla-domain-independent conformer of PC.Cross-reactivity to other vitamin K-aependent plasma proteins was examined by direct ELISA; HPC-2 and 3 reacted solely to PC, but HPC-1 and 4 also reacted with prothrombin and HPC-5 with both prothrombin and factor X.These findings indicated that there are two or more metal binding sites besides the Gla-domain, possibly one in the light chain and the other(s) in the heavy chain. The presence of these metal binding sites may contribute to the unique conformer of vitamin K-dependent plasma proteins including protein C.
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Stenflo, J., A.-K. öhlin, Å. Lundvall, and B. Dahlback. "β-HYDROXY ASPARTIC ACID AND ft-HYDROXYASPARAGINE IN THEEGF-HOMOLOGY REGIONS OF PROTEIN C AND PROTEINS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643995.
Full textAbstract:
The amino acid sequence has been determined for all of the vitamin K-dependent proteins and the gene structure is known for some of them. These findings have shown the proteins to consist of four clearly discernible domains, except protein S which has six domains. The protein domains seem to be coded on separate exons (Foster, D. C. et. al. 1985 Proc. Natl. Acad. Sci. USA 82,4673). The vitamin K-dependent γ-carboxyglutamic acid (Gla) containing domain isthe common structural denominator of the members of this protein family. In addition, all of these proteins except prothrombin contain domains that are homologous to the precursor of the epidermal growth factor (EGF). Such domains arealso found in proteins that are not vitamin K-dependent, such as the low density lipoprotein receptor, thrombomodulin, factor XII, plasminogen, the tissue type plasminogen activator, urokinase and the complement protein Clr. The vitamin K-dependent proteins can be dividedinto three groups. Factors VII, IX, X, protein C and protein Z form one group, which in addition to the Gla-region have two EGF-homology regions and one domain that is homologous to the serine proteases. Prothrombin has two 'kringle' structures and a serine protease domain and constitutes a group of its own. Protein S is also unique in that it has four EGF-homology regions and a COOH-terminal region that is homologous to the sexual hormone binding globulin (see poster by Edenbrand et. al.).Recently a posttranslationally modified amino acid, B-hydroxyaspatic acid (Hya), was identified in position 71 in the NH2-terminal EGF-homology region ofbovine protein C. The amino acid is formed by hydroxylation of aspartic acid. It has also been identified in the corresponding positions in factors VII, IX,X and protein Z (i. e. proteins which like protein C have two EGF-homology regions each). In protein S the N2-terminal of four EGF-homology regions has hydroxy lated aspartic acid .whereas the following three EGF-like domains have B-hydroxyasparagine. The nucleotide sequence codes for asparagine in the three latter positions. Neither vitamin K nor vitamin C seem to be involvedin the formation of the two hydroxylated amino acids. Recently, Hya was identified in acid hydrolysates of the complement protein Clr. Hya and Hyn have onlybeen found in domains that are homologous to the EGF precursor. In an attempt to identify the structural requirement of the hydroxylating enzyme, we have compared the sequences of EGF-homology regions that contain Hya or Hyn with the corresponding sequences that have been shown not to contain the modified amino acids. The domains that have Hya or Hyn have the consensus sequence Cx xxxx xCxC. This sequence has been found in three EGF-like domains in the EGF-precursor, in two in the LDL-receptor and in two in thrombomodulin. Furthermore, the neurogenic Notch locus in Drosophila melanogaster codes for 36 EGF-homolgy regions, 22 of which contain the consensussequence, whereas the Lin-12 locus in Caenorhabditis elegans codes for at least 11 EGF-like repeats, two of which comply with the consensus sequence. Whether any of these proteins contain Hya orHyn is not yet known with certainty.It has been hypothesized that Hya isinvolved in the Gla independent Ca2+binding of factors IX, X and protein C. In an attempt to resolve this issue, we have isolated the EGF-homology region from human protein C and been able to demonstrate that it binds Ca2+ (see poster by öhlin and Stenflo). However, we do not yet know whether Hya is directly involved in the Ca2+binding.
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Zhu, Feng, Yan Wang, Chaochao Chen, Guanfeng Liu, and Xiaolin Zheng. "A Graphical and Attentional Framework for Dual-Target Cross-Domain Recommendation." In Twenty-Ninth International Joint Conference on Artificial Intelligence and Seventeenth Pacific Rim International Conference on Artificial Intelligence {IJCAI-PRICAI-20}. California: International Joint Conferences on Artificial Intelligence Organization, 2020. http://dx.doi.org/10.24963/ijcai.2020/415.
Full textAbstract:
The conventional single-target Cross-Domain Recommendation (CDR) only improves the recommendation accuracy on a target domain with the help of a source domain (with relatively richer information). In contrast, the novel dual-target CDR has been proposed to improve the recommendation accuracies on both domains simultaneously. However, dual-target CDR faces two new challenges: (1) how to generate more representative user and item embeddings, and (2) how to effectively optimize the user/item embeddings on each domain. To address these challenges, in this paper, we propose a graphical and attentional framework, called GA-DTCDR. In GA-DTCDR, we first construct two separate heterogeneous graphs based on the rating and content information from two domains to generate more representative user and item embeddings. Then, we propose an element-wise attention mechanism to effectively combine the embeddings of common users learned from both domains. Both steps significantly enhance the quality of user and item embeddings and thus improve the recommendation accuracy on each domain. Extensive experiments conducted on four real-world datasets demonstrate that GA-DTCDR significantly outperforms the state-of-the-art approaches.
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Berkner, K. L., S. J. Busby, J. Gambee, and A. Kumar. "EXPRESSION IN MAMMALIAN CELLS OF FUSION PROTEINS BETWEEN HUMAN FACTORS IX AND VII." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643568.
Full textAbstract:
The vitamin K-dependent plasma proteins demonstrate remarkable similarities in their structures: all have multiple domains in common and extensive homology is observed within many of these domains. In order to investigate the structure-function relationship of these proteins, we have interchanged domains of one protein (factor IX) with that of another (factor VII) and have compared the expression of these fusion proteins with recombinant and native factors IX and VII. Oligonucleotide-directed mutagenesis was used to generate four fusion proteins: factor IX/VII-1, which contains the factor IX leader and gla domain fused to the growth factor and serine protease of factor VII; factor VII/IX-1, a reciprocal fusion protein of factor IX/VII-1; factor IX/VII-2, which contains the factor IX leader adjoined to the mature factor VII protein sequence; and factor VII/IX-2, the reciprocal fusion protein of factor IX/VII-2. The cDNAs encoding all four proteins were cloned into mammalian expression vectors, and to date three of these (factors IX/VII-1, 2 and VII/IX-1) have been transfected into baby hamster kidney (BHK) cells or 293 cells and characterized. Factors IX/VII-1 and VII/IX-1 were both secreted at levels comparable to recombinant factors IX and VII. The factor IX/VII-1 was identical in molecular weight to native or recombinant factor VII (i.e., 53 K). Factor VII/IX-1 was expressed as two proteins with molecular weights around 68 kd, as observed with recombinant factor IX. The factor IX/VII-1 protein has been purified to homogeneity and has been found to possess factor VII biological activity, but at a specific activity approximately 20% that of plasma factor VII. Thus, the gla domain of one clotting factor is capable of directing the activation of another and of generating biologically active protein. In contrast, no activity was observed with the factor IX/VII-2 fusion protein, indicating that there are limits to the interchanges which can generate functional blood clotting factors.
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Bermúdez, Alfredo, and Francisco Pena. "The Galerkin Lumped Parameter Method for Thermal Problems." In ASME 2012 11th Biennial Conference on Engineering Systems Design and Analysis. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/esda2012-83003.
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In this contribution, we present a method called Galerkin lumped parameter (GLP) method, as a generalization of the lumped parameter models used in engineering. This method can also be seen as a model-order reduction method. Similarities and differences are discussed. In the GLP method, introduced in [1], domain is decomposed into several sub-domains and a time-independent adapted reduced basis is calculated solving elliptic problems in each sub-domain. The method seeks a global solution in the space spanned by this basis, by solving an ordinary differential system. This approach is useful for electric motors, since the decomposition into several pieces is natural. Numerical results concerning heat equation are presented. Firstly, the comparison with an analytic solution is shown to check the implementation of the numerical algorithm. Secondly, the thermal behavior of an electric motor is simulated, assuming that the electric losses are known. A comparison with the solution obtained by the finite element method is shown.
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Freyssinet, J. M., A. Beretz, C. Klein-Soyer, J. Gauchy, J. Gauchy, S. Schuhler, and J. P. Cazenave. "INHIBITION OF HUMAN PROTEIN C ACTIVATION BY VITAMIN K-DEPENDENT PROTEINS, INVOLVEMENT OF THE γ-CARBOXIGLUTAMIC ACID DOMAIN IN DISTINCT INTERACTIONS WITH THE HUMAN THROMBIN-THROMBOMODULIN COMPLEX AND PHOSPHOLIPIDS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643647.
Full textAbstract:
Protein C (PC) activation by thrombin (T) occurs at the endothelial cell (EC) surface in the presence of thrombomodulin (TM). Reconstitution of purified TM into phospholipid (PL) vesicles results in an increased activation of PC but not of Gla-domainless-PC (GD-PC), a chymotryptic derivative of PC lacking the γ-carboxyglutamic acid domain (Gla-domain). We show that several human vitamin K-dependent proteins can interfere in the activation of human PC by the human T-TM complex either in the presence or in the absence of PL. Prothrombin fragment 1 (F1), peptide 1 -4.1, the N-terminal chymotryptic Gla-domain of prothrombin (F II), FI I and factor X (FX) were able to inhibit PC activation. They had no effect on the amidolytic activity of activated PC. Non-competitive inhibition was observed in the presence of 10 yM F1 when PC, at various concentrations, was activated by the 8 μM T-TM complex, at 2 mM Ca2+, with or without PL-reconstituted TM. In any case the apparent Km remained unchanged at 2 μM. In the presence of optimal PL concentrations and in the absence of F1, the Vmax could be enhanced up to 9-fold. When F1 was present, the extents of inhibition with and without PL were comparable and resulted in a 3fold decrease of the Vmax. These effects were independent of Ca2+ between 1 and 5 mM and of T between 10 and 50 nM. At 0.6 μM PC, half maximal inhibition occurred at 8μM F1 and 1 μM peptide 1-41 in the presence or in the absence of PL. Protein S and factors VII and IX had only minimal effect. The inhibition due to F1 and FX was also noticed when PC was activated by T in the presence of cultured human vascular EC. A Ki of 4 μM could be determined for F1 with EC-bound TM. The non-competitive character was confirmed by the observation that F1 could also inhibit the activation of GD-PC by the T-TM complex. Incomplete heat-decarboxylation of F1 and FII, partially abolished their capacity to inhibit PC activation. These results suggest that the Gla domain of PC is involved in two distinct types of interactions. This vitamin K-dependent functional entity is necessary to allow the enhancement of PC activation by anionic PL and also interacts with the T-TM complex.
Reports on the topic "Domaine Gla"
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Peterson, T. D., C. W. Jefferson, and A. Anand. Geological setting and geochemistry of the ca. 2.6 Ga Snow Island Suite in the central Rae Domain of the Western Churchill Province, Nunavut. Natural Resources Canada/ESS/Scientific and Technical Publishing Services, 2015. http://dx.doi.org/10.4095/296599.
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