title: Structural basis of coagulation factor V recognition for cleavage by RVV-V.
abstract: Russell's viper venom factor V (FV) activator (RVV-V) is a thrombin-like proteinase that specifically cleaves the Arg1545-Ser1546 bond of FV. Here we present the crystal structure of RVV-V in complex with the FV14 peptide (residues 1533-1546 of human FV) determined at 1.8Å resolution. The structure reveals multiple interactions between RVV-V and the seven residues, Ile1539 (P(7))-Arg1545 (P(1)), of the cleaved substrate. Comparison with substrate-free structures reveals conformational changes of the RVV-V loops upon substrate binding, suggesting that the multiple interactions are mediated by an induced-fit mechanism. The results provide an explanation for the narrow specificity of RVV-V.
authors.affiliation: Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nakayama
authors.forename: Youssef
authors.initials: Y
authors.lastname: Ben Ammar
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: Soichi
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000595:Amino Acid Sequence; D005165:Factor V / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D005165:Factor V; D012697:Serine Endopeptidases; C057675:snake venom factor V activator