Thrombin-like enzymes in snake venoms

Abstract

Snake venoms, particularly from vipers, are rich sources of serine proteinases, some of which contain thrombin-like activity. Following human envenomations, these toxins often produce rapid coagulopathies via the depletion of circulating fibrinogen, typically via specific proteolysis of the Aα and Bβ subunits. Hypofibrinogenemia following bites may be prolonged, contributing to hemorrhagic effects of the venom and occasionally leading to life-threatening conditions such as disseminated intravascular coagulation. However, they have also been used as therapeutic drugs for treating a diversity of human disorders, including strokes, deep vein thromboses and cerebral and myocardial infarctions. Many snake venom thrombin-like enzymes (SV-TLEs) have been sequenced, and important structural elements (six disulfides, the catalytic triad) are highly conserved. SV-TLEs are commonly glycosylated, and this modification may confer a high level of stability; unlike trypsin, they are exceptionally stable in aqueous solution. Structurally, they are closely related to other serine proteinases such as trypsin and chymotrypsin, but as a result of gene duplication, accelerated point mutations and ASSET, venom TLEs have evolved a diversity of activities. The relationship between structure and function of the different venom serine proteinases is still unclear, and future studies of substrate specificity of this diverse family of toxins will help resolve this uncertainty.