{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:03:05Z","timestamp":1792177385976,"version":"4.4.0"},"reference-count":88,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,6,28]],"date-time":"2006-06-28T00:00:00Z","timestamp":1151452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2006,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Blood coagulation factor V (FV) is a multifunctional protein that circulates in human plasma as a precursor molecule which can be activated by thrombin or activated factor X (FXa) in order to express its cofactor activity in prothrombin activation. FV activation is achieved by limited proteolysis after Arg709, Arg1018, and Arg1545 in the FV molecule. The venoms of <jats:italic>Daboia russelli<\/jats:italic> and <jats:italic>Daboia lebetina<\/jats:italic> contain a serine protease that specifically activates FV by a single cleavage at Arg1545. We have predicted the three\u2010dimensional structure of these enzymes using comparative protein modeling techniques. The plasminogen activator from <jats:italic>Agkistrodon acutus<\/jats:italic>, which shows a high degree of homology with the venom FV activators and for which a high\u2010quality crystallographic structure is available, was used as the molecular template. The RVV\u2010V and LVV\u2010V models provide for the first time a detailed and accurate structure of a snake venom FV activator and explain the observed sensitivity or resistance toward a number of serine protease inhibitors. Finally, electrostatic potential calculations show that two positively charged surface patches are present on opposite sides of the active site. We propose that both FV activators achieve their exquisite substrate specificity for the Arg1545 site via interactions between these exosites and FV. Proteins 2006. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.21051","type":"journal-article","created":{"date-parts":[[2006,6,28]],"date-time":"2006-06-28T22:35:40Z","timestamp":1151534140000},"page":"968-984","source":"Crossref","is-referenced-by-count":21,"title":["Structural models of the snake venom factor V activators from <i>Daboia russelli<\/i> and <i>Daboia lebetina<\/i>"],"prefix":"10.1002","volume":"64","author":[{"given":"Kenneth","family":"Segers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rosing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerry A.F.","family":"Nicolaes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,6,28]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000012665.51263.B7"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.14.4846"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204972200"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402107200"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109890"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)86616-4"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)86294-4"},{"key":"e_1_2_5_9_2","first-page":"241","article-title":"Factor V activation and inactivation by venom proteases","volume":"31","author":"Rosing J","year":"2001","journal-title":"Haemostasis"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0300-9084(00)01178-0"},{"key":"e_1_2_5_11_2","doi-asserted-by":"crossref","first-page":"12230","DOI":"10.1016\/S0021-9258(19)86454-2","article-title":"Molecular properties of the Factor V\u2010activating enzyme from Russell's viper venom","volume":"254","author":"Kisiel W","year":"1979","journal-title":"J Biol Chem"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(81)80024-9"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.18.6800"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615145"},{"key":"e_1_2_5_15_2","doi-asserted-by":"crossref","first-page":"6556","DOI":"10.1016\/S0021-9258(20)65178-X","article-title":"Thrombin\u2010catalyzed activation of human coagulation factor V","volume":"257","author":"Suzuki K","year":"1982","journal-title":"J Biol Chem"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)70079-9"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00457a004"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4838(98)00232-5"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1200"},{"key":"e_1_2_5_20_2","first-page":"123","article-title":"Proteases from Vipera lebetina venom affecting coagulation and fibrinolysis","volume":"31","author":"Siigur J","year":"2001","journal-title":"Haemostasis"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.36.21158"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00776a002"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00776a003"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00623a022"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1975.tb00853.x"},{"key":"e_1_2_5_26_2","doi-asserted-by":"crossref","first-page":"21864","DOI":"10.1016\/S0021-9258(18)54717-7","article-title":"Meizothrombin formation during factor Xa\u2010catalyzed prothrombin activation. 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