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Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake Bothrops atrox (Jergon) Induces Glycoprotein VI Shedding and Impairs Platelet Function.


ABSTRACT: Atroxlysin-III (Atr-III) was purified from the venom of Bothrops atrox. This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase. Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain. Its identity with bothropasin and jararhagin from Bothrops jararaca is 97% and 95%, respectively. Its enzymatic activity is metal ion-dependent. The divalent cations, Mg2+ and Ca2+, enhance its activity, whereas excess Zn2+ inhibits it. Chemical modification of the Zn2+-complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it. Atr-III degrades plasma fibronectin, type I-collagen, and mainly the ?-chains of fibrinogen and fibrin. The von Willebrand factor (vWF) A1-domain, which harbors the binding site for GPIb, is not hydrolyzed. Platelets interact with collagen via receptors for collagen, glycoprotein VI (GPVI), and ?2?1 integrin. Neither the ?2?1 integrin nor its collagen-binding A-domain is fragmented by Atr-III. In contrast, Atr-III cleaves glycoprotein VI (GPVI) into a soluble ~55-kDa fragment (sGPVI). Thereby, it inhibits aggregation of platelets which had been stimulated by convulxin, a GPVI agonist. Selectively, Atr-III targets GPVI antagonistically and thus contributes to the antithrombotic effect of envenomation by Bothrops atrox.

SUBMITTER: Oliveira LS 

PROVIDER: S-EPMC6803841 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Atroxlysin-III, A Metalloproteinase from the Venom of the Peruvian Pit Viper Snake <i>Bothrops atrox</i> (Jergón) Induces Glycoprotein VI Shedding and Impairs Platelet Function.

Oliveira Luciana S LS   Estevão-Costa Maria Inácia MI   Alvarenga Valéria G VG   Vivas-Ruiz Dan E DE   Yarleque Armando A   Lima Augusto Martins AM   Cavaco Ana A   Eble Johannes A JA   Sanchez Eladio F EF  

Molecules (Basel, Switzerland) 20190926 19


Atroxlysin-III (Atr-III) was purified from the venom of <i>Bothrops atrox</i>. This 56-kDa protein bears N-linked glycoconjugates and is a P-III hemorrhagic metalloproteinase. Its cDNA-deduced amino acid sequence reveals a multidomain structure including a proprotein, a metalloproteinase, a disintegrin-like and a cysteine-rich domain. Its identity with bothropasin and jararhagin from <i>Bothrops jararaca</i> is 97% and 95%, respectively. Its enzymatic activity is metal ion-dependent. The divalen  ...[more]

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