The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jergón) snake venom acts both on blood vessel ECM and platelets

Eladio F. Sanchez, Francisco S. Schneider, Armando Yarleque, Marcia H. Borges, Michael Richardson, Suely G. Figueiredo, Karla S. Evangelista, Johannes A. Eble

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59 Scopus citations

Abstract

We report the isolation and structure-function relationship of a 23kDa metalloproteinase named atroxlysin-I from the venom of the Peruvian Bothrops atrox (Jergón). Atroxlysin is a P-I metalloproteinase and contains 204 residues. Its proteolytic activity towards dimethylcasein is enhanced by Ca+2 but inhibited by EDTA, dithiothreitol, excessive Zn+2 and α2-macroglobulin. Unlike other structurally homologous P-I metalloproteinases, atroxlysin-I causes hemorrhages. To examine its hemorrhagic activity mechanistically, we studied its function in vitro and in vivo. It cleaved the Ala14-Leu15 and Tyr16-Leu17 bonds in oxidized insulin B-chain and specifically hydrolyzed the α-chains of fibrin(ogen) in a dose- and time-dependent manner. Atroxlysin-I cleaved plasma fibronectin and other extracellular matrix proteins (collagens I and IV) and the triple-helical fragment CB3 of collagen IV, but did not degrade laminin-111. Complementarily, the laminin and collagen binding integrins α7β1 and α1β1 were cleaved by atroxlysin. Even without catalytic activity atroxlysin-I inhibited collagen- and ADP-triggered platelet aggregation.

Original languageEnglish
Pages (from-to)9-20
Number of pages12
JournalArchives of Biochemistry and Biophysics
Volume496
Issue number1
DOIs
StatePublished - Apr 2010

Bibliographical note

Funding Information:
The authors thank to Drs. M.R. Fontes and A.A. Takeda (Dept. of Physics and Biophysics, UNESP, Saõ Paulo, Brazil) for the determination of CD spectra. We also thank Mr. G. Naumann for his technical assistance with zinc analysis. This work was supported by FAPEMIG Grants No: CBB 359/06 and APQ-2673-40.1/07 to E.F.S., J.A.E. receives financial support of the DFG (Grants: SFB 815 project A6, SFB/TR23 project A8 and the Excellence Cluster Cardio-Pulmonary System).

Keywords

  • Atroxlysin
  • Hemostasis
  • Metalloproteinase
  • Platelets
  • Snake venom

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