Snake venom protein C activator

Protein C (PROC) is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids. It is synthesized as a single chain precursor, which is cleaved into a light chain and a heavy chain held together by a disulfide bond. In healthy organisms, the enzyme is activated by thrombin, which cleaves a tetradecapeptide from the amino end of the heavy chain; this reaction, which occurs at the surface of endothelial cells, is strongly promoted by thrombomodulin.

Venoms from Viperidae snakes contain serine proteinases that activate protein C by cleaving its heavy chain in a thrombomodulin-independent manner. It thus decreases/prevents blood coagulation.


Figure: Blood coagulation cascade and activity of protein C as an inhibitor of factors Va and VIIIa (image modified from Biochemistry, 4th edition, lubert stryer, standford university, freeman and company, new york, chapter 10, fig. 10-26).