Factor V Activation and Inactivation by Venom Proteases

Abstract

Blood coagulation factor V is a single-chain glycoprotein with M_r = 330,000 which plays an important role in the procoagulant and anticoagulant pathways. Thrombin activates factor V into factor Va, a two-chain molecule which is composed of a heavy (M_r = 105,000) and a light chain (M_r = 71,000/74,000). Factor Va accelerates factor Xa-catalysed prothrombin activation more than 1,000-fold and under physiological conditions the cofactor activity of factor Va in prothrombin activation is down-regulated by activated protein C. Factor V can also be activated by a wide variety of snake venoms (e.g. from Vipera species, Naja naja oxiana, Bothrops atrox) and by proteases present in the bristles of a South American caterpillar (Lonomia achelous). Some venoms, notably of Vipera lebetina turanica and Lonomia achelous, contain proteases that are able to inactivate factor V or factor Va. Venom factor V activators are excellent tools in studying the structure-function relationship of factor V(a) and they are also used in diagnostic tests for quantification of plasma factor V levels and for the screening of defects in the protein C pathway. In this review, the structural and functional properties of animal venom factor V activators and inactivators is described.

Snake venom thrombin-like enzymes: from reptilase to now

“…[12]. This SVTLE is able to activate factor V, a glycoprotein that plays an important role in the procoagulant and anticoagulant pathways [95], with a rate 250 -500-fold lower than thrombin ( fig. 4).…”

Serine Proteases Affecting Blood Coagulation and Fibrinolysis from Snake Venoms

“…Some venom proteases also activate the protein cofactor, factor V. For example, RVV-V (Daboia russelli) and thrombocytin (Bothrops atrox) activate factor V, the cofactor in the prothrombinase complex (reviewed in [3,4] ).…”

Activation of Factor v by Venom Proteases

“…This latter activity was approximately 25-fold lower than the activating activity. This was concluded from the times required to obtain half-maximal activation of factor V and inactivation of factor Va in experiments that specifically probed the activation or inactivation of factor V(a) by LVV-V (Rosing et al, 2001). Simultaneous/consecutive activation and inactivation of coagulation factor V by venoms is not unique for LVV, as it was reported earlier that a commercial protein C activator from the venom of Deinagkistrodon contortrix contortrix can both activate and inactivate factors V and VIII (Gable et al, 1997).…”

“…Siigur and coworkers have purified and characterized the factor V activator from Vipera lebetina and have shown that this protease, like RVV-V, cleaves the factor V molecule at the Arg 1545 -Ser 1546 peptide bond (Siigur et al, 1998(Siigur et al, , 1999. In our laboratory, we compared the factor V activators from Daboia russelli, Vipera lebetina, and Vipera ursini, abbreviated RVV-V, LVV-V, and UVV-V, respectively (Rosing et al, 2001). The proteases have been purified to homogeneity (see Figure 5), and the apparent molecular weights determined were 29 kDa for V. lebetina and D. russelli and 34 kDa for V. ursini.…”