Interaction of Bothrojaracin with Prothrombin

Russolina B. Zingali, M. Lucia Bianconi, Robson Q. Monteiro
2001 Pathophysiology of Haemostasis and Thrombosis  
Bothrojaracin (BJC) is a 27-kD protein from Bothrops jararaca venom that interacts with ·-thrombin (K D = 0.7 nM) through both anionbinding 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
more » ... 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 ·-thrombin, and (2) inhibition of prothrombin activation through interaction with proexosite I.
doi:10.1159/000048073 pmid:11910195 fatcat:yvuhppt2x5e75ijsyd2wgfbqje