Coagulation Factor X-Binding Protein fromDeinagkistrodon acutusVenom Is a Gla Domain-Binding Protein†

Biochemistry ◽  
1998 ◽  
Vol 37 (50) ◽  
pp. 17361-17370 ◽  
Author(s):  
Hideko Atoda ◽  
Midori Ishikawa ◽  
Hiroshi Mizuno ◽  
Takashi Morita
Keyword(s):  
Binding Protein ◽  
Coagulation Factor ◽  
Factor X ◽  
Gla Domain

scholarly journals Effective electrostatic charge of coagulation factor X in solution and on phospholipid membranes: implications for activation mechanisms and structure–function relationships of the Gla domain

1998 ◽  
Vol 330 (1) ◽  
pp. 533-539 ◽  
Author(s):  
P. Maria McGEE ◽  
Hoa TEUSCHLER ◽  
Jie LIANG
Keyword(s):  
Ionic Strength ◽  
Electrostatic Interactions ◽  
Specific Interaction ◽  
Geometric Analysis ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Reaction Rates ◽  
Phase Cell ◽  
Factor X ◽  
Gla Domain

Electrostatic interactions during activation of coagulation factor X were analysed by comparing effects of ionic strength on reaction rates with predictions of classical electrostatic theory. Geometrical correlations were investigated using alpha-shape-based computations on the crystal structure of Ca-fragment 1 of prothrombin. The ionic strength of the reaction environment was controlled with different univalent salts including NaCl, KCl, CsCl, LiCl, NaI, NaBr and KI. Reactions were assembled in three different environments: aqueous phase, cell membranes and synthetic TF/PS/PC (tissue factor relipidated in 30% phosphatidylserine, 70% phosphatidylcholine) vesicles. Reaction rates were measured at pH 7.2, 4 mM CaCl2 and 33 °C, using chromogenic substrate to follow factor Xa generation. Rates decreased with increasing concentration of univalent salt, and the magnitude of the decrease was independent of salt type. On the basis of electrostatic relationships on PS/PC vesicles, the effective charge on factor X was +1.5, and the PS/factor X stoichiometry was 2.28. Structural analysis of the γ-carboxyglutamic acid (Gla) domain revealed three surface pockets, forming potential sites for Ca2+ binding, with distinct spatial orientations. Interpreted together, the results of the geometric analysis and the measured effective charges suggest an efficient electrostatic mechanism for capture and retention of substrates by procoagulant membranes. Non-specific and delocalized interaction between the membrane and each one of the charged facets of the Gla domain can increase the probability of substrate binding, while allowing rotational and translational mobility of substrate for specific interaction with the enzyme.

Characterization of a homozygous Gly11Val mutation in the Gla domain of coagulation factor X

2009 ◽  
Vol 124 (1) ◽  
pp. 144-148 ◽  
Author(s):  
Ouerdia Chafa ◽  
Madjid Tagzirt ◽  
Jacqueline Tapon-Bretaudière ◽  
Abderrezak Reghis ◽  
Anne-Marie Fischer ◽  
...  
Keyword(s):  
Coagulation Factor ◽  
Factor X ◽  
Gla Domain
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