Snake Venom Proteases, Structure-Function Relationship and Effects on Blood Coagulation

Abstract

Snake venoms are probably the most highly concentrated secretion products found in vertebrate. Furthermore, proteases are in a unique position in snake venoms, especially in Crotalid and Viperid venoms. Biologically, proteolytic enzymes may contribute in two ways: the immobilization of the prey and the digestion of prey organism. They are responsible for the hemorrhage, shock, or disorder of blood coagulation after envenomation. They act, by activating, inactivating, or other converting effects, on almost all the components of hemostatic and fibrinolytic systems. Biochemically, they can be mainly classified into two groups: serine proteases, which are inhibited by phenylmethanesulfonyl fluoride (PMSF) and diisopropyl fluorophosphate (DFP). Their sequences are homologous to trypsin-kallikrein serine proteases. They share a common active site geometry and enzymatic mechanism but variation of primary sequences out of active center results in the differences of substrate specificities and further the difference of biological and pharmacological activities. Metalloproteinases, which are inhibited by metal chelating reagent (EDTA), are zinc-dependent. Up to now, sequence data indicate that they belong to a new metalloproteinase subfamily which has no significant sequence similarities with any other know metalloproteinases except for a conservative zinc-chelating sequence His-Glu-X-X-His. Because of their common and unique properties compared to their physiological corresponding factors, snake venom proteases have find a position uniquely in hemostasis and thrombosis, both in research and application.