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Titolo:
THE ROLE OF CALCIUM-IONS IN FACTOR-X ACTIVATION BY THROMBIN-E192Q
Autore:
LEBONNIEC BF; GUINTO ER; ESMON CT;
Indirizzi:
OKLAHOMA MED RES FDN,HOWARD HUGHES MED INST,825 NE 13 OKLAHOMA CITY OK 73104 OKLAHOMA MED RES FDN,CARDIOVASC BIOL RES PROGRAM OKLAHOMA CITY OK 73104 UNIV OKLAHOMA,HLTH SCI CTR,DEPT PATHOL OKLAHOMA CITY OK 73190 UNIV OKLAHOMA,HLTH SCI CTR,DEPT BIOCHEM OKLAHOMA CITY OK 73190
Titolo Testata:
The Journal of biological chemistry
fascicolo: 10, volume: 267, anno: 1992,
pagine: 6970 - 6976
SICI:
0021-9258(1992)267:10<6970:TROCIF>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
BOVINE FACTOR-X; GAMMA-CARBOXYGLUTAMIC ACID; COAGULATION FACTOR-X; PROTEIN-C; BLOOD-COAGULATION; HUMAN THROMBOMODULIN; CA-2+ BINDING; FACTOR-V; SPECIFICITY; REGION;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
B.F. Lebonniec et al., "THE ROLE OF CALCIUM-IONS IN FACTOR-X ACTIVATION BY THROMBIN-E192Q", The Journal of biological chemistry, 267(10), 1992, pp. 6970-6976

Abstract

Despite considerable sequence similarities, blood coagulation serine proteases exhibit remarkable specificity with respect to which zymogenthey activate. The basis for this specificity presumably involves recognition of a short sequence within the extended binding pocket of theenzyme, other interactions remote from the catalytic groove, and modulation by a definite protein cofactor. In addition, Ca2+ plays a majorrole in most activation processes, but, because both the enzyme and its substrate interact with Ca2+, whether Ca2+ influences the substrate, the enzyme, or both remains an open question. Thrombin is not a factor X-activating enzyme, but when Glu192, 3 residues remote from the active Ser195, is replaced with glutamine, the resultant serine protease(E192Q) becomes a bovine, but not human, factor X activator. Kinetic experiments with peptides corresponding to human and bovine factor X activating sites reveal that threonine at position P2 in human (versus a valine in bovine) accounts for the species specificity. Substitutionof the threonine in P2 of the human sequence with valine allows E192Qto cleave the human peptide whereas substitution of the valine in P2 of the bovine sequence with threonine hinders E192Q catalysis. Thrombin has no high affinity Ca2+ binding sites, and E192Q proteolysis of these peptides is not altered by Ca2+. The influence of Ca2+ in E192Q-mediated factor X activation provides therefore new insights into the role of the different Ca2+ binding sites in factor X. With factor X as substrate, the addition of Ca2+ enhances K(cat) 4-fold but increases K(m) 10-fold. When the vitamin K-dependent gamma-carboxyglutamic acid domain of factor X is removed, the K(m) remains high with or without Ca2 whereas K(cat) still increases upon addition of the metal ion. Theseresults suggest that factor X undergoes two metal-dependent transitions that influence the presentation of the activation site to activators.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 06:44:25