title: 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.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute, University of Maastricht, PO Box 616, NL-6200 MD Maastricht, The Netherlands. j.rosing@bioch.unimaas.nl
authors.forename: J
authors.initials: J
authors.lastname: Rosing
authors.forename: J W
authors.initials: JW
authors.lastname: Govers-Riemslag
authors.forename: L
authors.initials: L
authors.lastname: Yukelson
authors.forename: G
authors.initials: G
authors.lastname: Tans
mesh_terms: D000818:Animals; D010450:Endopeptidases / Q000737:chemistry / Q000494:pharmacology*; D005165:Factor V / Q000187:drug effects* / Q000378:metabolism; D015943:Factor Va / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D012910:Snake Venoms / Q000737:chemistry / Q000201:enzymology* / Q000494:pharmacology; D014688:Venoms / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D012910:Snake Venoms; D014688:Venoms; D015943:Factor Va; D005165:Factor V; D010450:Endopeptidases