| Autor: |
Oliveira LS; Research and Development Center, Ezequiel Dias Foundation, 30510-010 Belo Horizonte, MG, Brazil. luciana.oliveira@funed.mg.gov.br., Estevão-Costa MI; Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Münster, Germany. mina.estevao@gmail.com., Alvarenga VG; Research and Development Center, Ezequiel Dias Foundation, 30510-010 Belo Horizonte, MG, Brazil. valeria.alvarenga@funed.mg.gov.br., Vivas-Ruiz DE; Laboratorio de Biología Molecular-Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Av. Venezuela Cdra 34 S/N, Ciudad Universitaria, Lima 01, Lima 14-0576, Peru. dvivasr@unmsm.edu.pe., Yarleque A; Laboratorio de Biología Molecular-Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Av. Venezuela Cdra 34 S/N, Ciudad Universitaria, Lima 01, Lima 14-0576, Peru. ayarlequec@unmsm.edu.pe., Lima AM; Laboratory of Hemodynamics and Cardiovascular Technology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland. augusto.martinslima@epfl.ch., Cavaco A; Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Münster, Germany. acmcavaco@gmail.com., Eble JA; Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Münster, Germany. johannes.eble@uni-muenster.de., Sanchez EF; Research and Development Center, Ezequiel Dias Foundation, 30510-010 Belo Horizonte, MG, Brazil. eladio.flores@funed.mg.gov.br. |
| Abstrakt: |
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, Mg 2+ and Ca 2+ , enhance its activity, whereas excess Zn 2+ inhibits it. Chemical modification of the Zn 2+ -complexing histidine residues within the active site by using diethylpyrocarbonate (DEPC) inactivates it. Atr-III degrades plasma fibronectin, type I-collagen, and mainly the α-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 α2β1 integrin. Neither the α2β1 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 . |
