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. © 2010 Elsevier Inc.
Sanchez, E. F., Schneider, F. S., Yarleque, A., Borges, M. H., Richardson, M., Figueiredo, S. G., Evangelista, K. S., & Eble, J. A. (2010). The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jergón) snake venom acts both on blood vessel ECM and platelets. Archives of Biochemistry and Biophysics, 9-20. https://doi.org/10.1016/j.abb.2010.01.010