Biomaterial Database

Calcium enhances factor Xa activity independent of gamma-carboxyglutamic acid residues. 1988

G B Sherrill, and J B Meade, and T Kalayanamit, and D M Monroe, and F C Church

Division of Hematology, University of North Carolina School of Medicine, Chapel Hill 27599.

We investigated the gamma-carboxyglutamic acid (Gla) independent effect of calcium on the activity of human factor Xa. The effect of calcium on the reaction rate of factor Xa was compared using native and Gla-modified forms of human factor Xa [chemically decarboxylated (Gla-modified, 10 Gla residues modified/mol) and Gla-domainless (chymotrypsin-treated)]. Factor Xa activity was assessed by hydrolysis of a synthetic tripeptide nitroanilide substrate, by p-aminobenzamidine binding to the active site and by inhibition with antithrombin III. Calcium (1 mM) increased, by 25-35%, the amidolytic hydrolysis rates of all three factor Xa derivatives. Calcium had an apparent Kd of approximately 200 uM with both native and modified forms of factor Xa. However, there was no change in binding of p-aminobenzamidine, a small fluorescent probe, to factor Xa in the presence of calcium. Calcium (1 mM) increased the inhibition reaction rates of native and modified forms of factor Xa with antithrombin III by 20-30%. Magnesium (1 mM) showed greatly reduced effects on factor Xa activity relative to activities with calcium. We conclude that Gla-independent calcium interactions with factor Xa are important for some catalytic activities of this blood coagulation protease.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D009842	Oligopeptides	Peptides composed of between two and twelve amino acids.	Oligopeptide
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000990	Antithrombin III	A plasma alpha 2 glycoprotein that accounts for the major antithrombin activity of normal plasma and also inhibits several other enzymes. It is a member of the serpin superfamily.	Heparin Cofactor I,Antithrombin III-Alpha,Atenativ,Heparin Co-Factor I,Kybernin,Serpin C1,Thrombate III,Antithrombin III Alpha,Antithrombin IIIAlpha,Cofactor I, Heparin,Heparin Co Factor I
D001550	Benzamidines	Amidines substituted with a benzene group. Benzamidine and its derivatives are known as peptidase inhibitors.
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012697	Serine Endopeptidases	Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.	Serine Endopeptidase,Endopeptidase, Serine,Endopeptidases, Serine
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D015055	1-Carboxyglutamic Acid	Found in various tissues, particularly in four blood-clotting proteins including prothrombin, in kidney protein, in bone protein, and in the protein present in various ectopic calcifications.	gamma-Carboxyglutamate,gamma-Carboxyglutamic Acid,3-Amino-1,1,3-propanetricarboxylic Acid,1 Carboxyglutamic Acid,gamma Carboxyglutamate,gamma Carboxyglutamic Acid