Interaction of bothrojaracin with prothrombin.
Bothrojaracin (BJC) is a 27-kD protein from Bothrops jararaca venom that interacts with alpha-thrombin (K(D) = 0.7 nM) through both anion-binding exosites I and II. Recently, it has been shown that BJC interacts with the exosite I precursor (proexosite I) on human prothrombin (K(D) = 75 nM), forming a 1:1 Ca(2+)-independent noncovalent complex with the zymogen. Complex formation was associated with inhibition of zymogen activation by Oxyuranus scutellatus venom. In addition, BJC strongly decreased the prothrombin activation by factor Xa only in the presence of factor Va. A similar effect was observed in the presence of phospholipids, suggesting that BJC specifically inhibits the interaction of prothrombin with factor Va. It is proposed that BJC has two independent mechanisms for anticoagulation: (1) inhibition of exosite-I-dependent activities on alpha-thrombin, and (2) inhibition of prothrombin activation through interaction with proexosite I.
Zingali
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RB
Departamento de Bioquímica Médica/ICB/CCS, Bloco H-2o Andar-Ilha do Fundao, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brazil. lzingali@bioqmed.ufrj.br
Bianconi
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ML
Monteiro
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RQ
D000818:Animals; D000925:Anticoagulants / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D001665:Binding Sites; D003435:Crotalid Venoms / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D011516:Prothrombin / Q000378:metabolism*; D013917:Thrombin / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D003435:Crotalid Venoms; C083739:bothrojaracin; D011516:Prothrombin; D013917:Thrombin