The Intriguing World of Prothrombin Activators from Snake Venom

Activation of prothrombin to mature thrombin occurs by the proteolytic action of the prothrombinase complex consisting of a serine proteinase factor Xa, and cofactors factor Va, Ca(2+) ions and phospholipids. Several exogenous prothrombin activators are found in snake venom. They are classified into four groups based on their cofactor requirements. Group A and B prothrombin activators are metalloproteinases whereas group C and D prothrombin activators are serine proteinases. Group C prothrombin activators resemble the mammalian factor Xa-factor Va complex, while Group D activators are structurally and functionally similar to factor Xa. This review provides a detailed description of the current knowledge on all prothrombin activators and highlights several intriguing questions that are yet to be answered.