The effect of post-translational modifications on the hemorrhagic activity of snake venom metalloproteinases

The effect of post-translational modifications on the hemorrhagic activity of snake venom metalloproteinases

Author Garcia, L. T. Google Scholar
Silva, LTPE Google Scholar
Ramos, OHP Google Scholar
Carmona, A. K. Google Scholar
Bersanetti, P. A. Google Scholar
Selistre-de-Araujo, H. S. Google Scholar
Institution Universidade Federal de São Carlos (UFSCar)
Universidade Federal de São Paulo (UNIFESP)
Abstract Metalloproteinases (MPs) are Zn+-dependent endoproteolytic enzymes, abundant in crotalid and viperid snake venoms. Most snake venom metalloproteinases (svMPs) are active on extracellular matrix components and this effect is thought to result in bleeding as a consequence of the basement membrane disruption in capillaries. Jararhagin and ACLH are hemorrhagic svMPs from Bothrops jararaca and Agkistrodon contortrix laticinctus venom, respectively. Both enzymes demonstrate proteolytic activity on fibrinogen and fibronectin and jararhagin inhibits collagen-induced platelet aggregation in vitro. This work describes the expression, purification and successful refolding of the recombinant ACLH zymogen (rPRO-ACLH) as well as the catalytic domain of jararhagin (rCDJARA). the heterologous proteins were produced in E. coli, an in vivo expression system that does not make post-translational modifications. the recombinant refolded proteins did not show any hemorrhagic activity in mice skin, as well as the native deglycosylated jararhagin and ACLH. However, they preserved their proteolytic activity on fibrinogen and fibronectin. It seems that the hemorrhagic properties of these hemorrhagins are dependent on post-translational modifications, whereas their proteolytic activity is not dependent on such modifications. (C) 2004 Elsevier Inc. All rights reserved.
Keywords ACLH
glycosylation
hemorrhage
jararhagin
metalloproteinase
snake venom
post-translational modification
Bothrops
Language English
Date 2004-05-01
Published in Comparative Biochemistry and Physiology C-toxicology & Pharmacology. New York: Elsevier B.V., v. 138, n. 1, p. 23-32, 2004.
ISSN 1532-0456 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 23-32
Origin http://dx.doi.org/10.1016/j.cca.2004.04.004
Access rights Closed access
Type Article
Web of Science ID WOS:000223703800004
URI http://repositorio.unifesp.br/handle/11600/27727

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