PROTHROMBIN ACTIVATION BY SNAKE-VENOM PROTEASES

Snake venom prothrombin activators can be classified into four groups on the basis of their structural and functional properties in prothrombin activation. Group I activators (the best known example of which is the activator present in Echis carinatus venom) are metalloproteases that efficiently convert prothrombin into meizothrombin. Prothrombin activation by these activators is not affected by the presence of the prothrombinase cofactors, negatively charged phospholipids, CaCl2 or factor Va. Group II activators (e.g. the Notechis scutatus scutatus activator) are serine proteases that require the presence of negatively charged phospholipids CaCl2 and factor Va for efficient prothrombin activation. Activators belonging to group III (e.g. Oxyuranus scutellatus scutellatus) are serine proteases that are also stimulated by negatively charged phospholipids and CaCl2 but not by factor Va. These activators have a high molecular weight (Mr > 250,000) and are composed of a catalytic unit that is tightly associated with a factor Va-like cofactor unit. An additional group of activators can be defined that consists of snake venoms which do not activate prothrombin but which convert prothrombin into inactive precursor forms of thrombin In this review we describe a representative example of each group using experimental techniques currently available for the analysis of prothrombin activation