Publicação: Crystal structure of Bn IV in complex with myristic acid: A Lys49 myotoxic phospholipase A(2) from Bothrops neuwiedi venom
Carregando...
Arquivos
Data
2011-03-01
Orientador
Coorientador
Pós-graduação
Curso de graduação
Título da Revista
ISSN da Revista
Título de Volume
Editor
Elsevier France-editions Scientifiques Medicales Elsevier
Tipo
Artigo
Direito de acesso
Acesso aberto
Resumo
The LY549-PLA(2)s myotoxins have attracted attention as models for the induction of myonecrosis by a catalytically independent mechanism of action. Structural studies and biological activities have demonstrated that the myotoxic activity of LYS49-PLA(2) is independent of the catalytic activity site. The myotoxic effect is conventionally thought to be to due to the C-terminal region 111-121, which plays an effective role in membrane damage. In the present study, Bn IV LYS49-PLA(2) was isolated from Bothrops neuwiedi snake venom in complex with myristic acid (CH3(CH2)(12)COOH) and its overall structure was refined at 2.2 angstrom resolution. The Bn IV crystals belong to monoclinic space group P2(1) and contain a dimer in the asymmetric unit. The unit cell parameters are a = 38.8, b = 70.4, c = 44.0 angstrom. The biological assembly is a "conventional dimer" and the results confirm that dimer formation is not relevant to the myotoxic activity. Electron density map analysis of the Bn IV structure shows clearly the presence of myristic acid in catalytic site. The relevant structural features for myotoxic activity are located in the C-terminal region and the Bn IV C-terminal residues NKKYRY are a probable heparin binding domain. These findings indicate that the mechanism of interaction between Bn IV and muscle cell membranes is through some kind of cell signal transduction mediated by heparin complexes. (C) 2010 Elsevier Masson SAS. All rights reserved.
Descrição
Palavras-chave
Idioma
Inglês
Como citar
Biochimie. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 93, n. 3, p. 513-518, 2011.
