Artículos de revistas
Crystal structures of BnSP-7 and BnSP-6, two Lys49-phospholipases A(2): quaternary structure and inhibition mechanism insights
Fecha
2003-11-21Registro en:
Biochemical and Biophysical Research Communications. San Diego: Academic Press Inc. Elsevier B.V., v. 311, n. 3, p. 713-720, 2003.
0006-291X
10.1016/j.bbrc.2003.10.047
WOS:000186643100026
Autor
Universidade Estadual Paulista (Unesp)
UNAERP
Universidade de São Paulo (USP)
Institución
Resumen
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.