Two coagulation factor X activators from Vipera a. ammodytes
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- 作者：Adrijana Leonardi ; Jay W. Fox ; Alenka Trampuš ; -Bakija ; Igor Križ ; aj
- 关键词：Snake venom ; Vipera ammodytes ammodytes ; Metalloproteinase ; Coagulation factor X activator ; Procoagulant
- 刊名：Toxicon
- 出版年：2008
- 出版时间：October 2008
- 年：2008
- 卷：52
- 期：5
- 页码：628-637
- 全文大小：639 K
文摘
Two activators of coagulation factor X, 58 kDa VAFXA-I and 70 kDa VAFXA-II, were purified from the venom of long-nosed viper (Vipera ammodytes ammodytes) by chromatography on gel filtration, affinity, ion-exchange and hydroxyapatite media. Both enzymes are glycoproteins composed of a heavy chain and two C-type lectin-like light chains all joined by disulphide bonds. LC–MS and LC–MS/MS analysis of their tryptic fragments demonstrated that the heavy chain consists of three domains, metalloproteinase, disintegrin-like and cysteine-rich domains. The partial amino acid sequences of VAFXAs are very similar to those of the known factor X activators, RVV-X from Vipera russelli and VLFXA from Vipera lebetina venoms, as well as to other members of the reprolysin family of metalloproteinases. The VAFXAs activate factor X in a Ca2+-dependent manner with the same specificity as physiological activators. The activators weakly hydrolyzed insulin B-chain, fibrinogen and some components of the extracellular matrix in vitro, but did not activate prothrombin or plasminogen. VAFXAs inhibit collagen-induced platelet aggregation in vitro. They activate coagulation factor X to Xa without toxic effects. Their application in treating patients with dysfunctional factors IXa or VIIa to restore the normal blood coagulation process is thus promising.