Crystal structures of BnSP-7 and BnSP-6, two Lys49-phospholipases A(2): quaternary structure and inhibition mechanism insights

Nenhuma Miniatura disponível

Data

2003-11-21

Autores

Magro, A. J.
Soares, A. M.
Giglio, JR
Fontes, MRM

Título da Revista

ISSN da Revista

Título de Volume

Editor

Elsevier B.V.

Resumo

Phospholipases A(2) are components of Bothrops venoms responsible for disruption of cell membrane integrity via hydrolysis of its phospholipids. A class of PLA(2)-like proteins has been described which despite PLA(2) activity on artificial substrate, due to a D49K mutation, is still highly myonecrotic. This work reports the X-ray structure determination of two Lys49-PLA(2)s from Bothrops neuwiedi pauloensis (BnSP-7 and BnSP-6) and, for the first time, the comparison of eight dimeric Lys49-PLA2s. This comparison reveals that there are not just two (open and closed) but at least six different conformations. The binding of fatty acid observed in three recent Lys49-PLA(2) structures seems to be independent of their quaternary conformation. Cys29 polarization by Lys122 is not significant for BnSP-7 and BnSP-6 or other structures not bound by fatty acids. These structures may be in an active state when nothing is bound to them and the Lys122/Cys29 interactions are weak or absent. (C) 2003 Elsevier B.V. All rights reserved.

Descrição

Palavras-chave

phospholipase A(2), myotoxin, crystal structure, bothropic venom, quaternary structure changes, lack of catalytic mechanism

Como citar

Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc. Elsevier B.V., v. 311, n. 3, p. 713-720, 2003.