Structure and function of snake venom metalloproteinase family

Abstract

Venoms of snakes belonging to families Viperidae (viper) and Crotalidae (pit viper) produce striking local effects, consisting of hemorrhage, necrosis, and edema, and often induce marked alterations of blood coagulation system as well (Iwanaga and Suzuki, 1979). Among these pathological effects, hemorrhage is a most common occurrence in a victim bitten by crotalid and viperid snakes and various components, such as hemorrhagic factors and metalloproteinases, involved in these venoms have been isolated and characterized (Osaka, 1979). The hemorrhagic metalloproteinases cause localized hemorrhage by direct action on the blood vessel wall. Electron microscopic studies indicate that erythrocytes are leaked in a one-by-one fashion through widened inter-endothelial gaps when capillaries are exposed to these hemorrhagic proteins. Hemorrhagic metalloproteinases degrade basement membrane preparation, in addition to the isolated components including type IV collagen, laminin, nidogen, and fibronectin (Baramova et al., 1989). The enzymes may disrupt the pericellular basement membrane through a proteolytic activity and with subsequent damage to the integrity of the vessel wall after which hemorrhage occurs. On the other hand, crotalid and viperid venoms contain an abundance of metalloproteinases which are completely free from hemorrhagic activity (Iwanaga et al., 1976). Some of them have originally been reported as anticoagulant proteases with fibrinogenolytic or fibrinolytic activity (Markland, 1991). Additional group of venom metalloproteinases are procoagulants having very strict substrate specificities. Two well known examples of this type are Russell’s viper venom factor X activator (RVV-X) and Echis carinatus venom prothrombin activator (Morita and Iwanaga, 1981; Furie and Furie, 1976).