CHARACTERIZATION OF TWO MAJOR FAMILIES OF FIBRINOGENOLYTIC PROTEASES FROM THE VENOM OF TAIWAN HABU WITH SPECIAL REFERENCE TO THEIR MEDICAL APPLICATIONS

Abstract

Venoms from various snake species alter the haemostatic and blood coagulation systems of human victims or experimental animals in a complex manner. Different venoms contain multiple components that behave as pro- or anticoagulants, which directly (or indirectly) induce or inhibit fibrinogen and/or platelet aggregation and related complex biochemical processes, resulting in common clinical complications of blood clotting or uncontrolled hemorrhage by envenomation of snakebites. Two major families of venom proteases with fibrinogenolytic activity have been isolated and characterized from the venom of Taiwan habu (Trimeresurus mucrosquamatus), one major crotalid snake species in Taiwan. In this account we will review the structures of one venom metalloproteinase and its complex with the endogenous peptide inhibitors as revealed by X-ray crystallography. We will also report another kallikrein-like protease family with strong β-fibrinogenolytic activities in vitro and hypotensive activity in vivo. It is deemed necessary and essential to isolate these venom enzymes that are responsible for the fibrinogen-degrading activities that destroy the precursor fibrinogen molecules with the result of excluding the formation of fibrin clot in blood plasma. The structural work by crystallographic studies of these proteases may provide some insights into the rational design of thrombolytic or antihypertension drugs that bind to the active sites of these clinically useful venom proteases.

Keywords: :

• Fibrinogenolytic proteases
• Venom metalloproteinase
• Kallikrein-like protease
• Thrombosis
• Hypertension
• Crotalidae snakes.