The novel metalloproteinase atroxlysin-I from Peruvian Bothrops atrox (Jergón) snake venom acts both on blood vessel ECM and platelets
| Autor: | Johannes A. Eble, Márcia Helena Borges, Suely G. Figueiredo, Eladio F. Sanchez, Michael K. Richardson, Armando Yarleque, Francisco Santos Schneider, Karla S. Evangelista |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Blood Platelets
Integrins Integrin Molecular Sequence Data Biophysics Hemorrhage Matrix metalloproteinase Biochemistry Dithiothreitol Substrate Specificity Extracellular matrix chemistry.chemical_compound Laminin Macroglobulins Animals Humans Bothrops Amino Acid Sequence Molecular Biology Metalloproteinase Fibrin Hemostasis biology Chemistry Fibrinogen Extracellular Matrix Fibronectins Fibronectin Snake venom biology.protein Metalloproteases Blood Vessels Snake Venoms |
| Zdroj: | Archives of biochemistry and biophysics. 496(1) |
| ISSN: | 1096-0384 |
| Popis: | We report the isolation and structure–function relationship of a 23 kDa metalloproteinase named atroxlysin-I from the venom of the Peruvian Bothrops atrox (Jergon). 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 Ala 14 –Leu 15 and Tyr 16 –Leu 17 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 α 7 β 1 and α 1 β 1 were cleaved by atroxlysin. Even without catalytic activity atroxlysin-I inhibited collagen- and ADP-triggered platelet aggregation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect