dc.contributor | Universidade Estadual Paulista (Unesp) | |
dc.contributor | Universidade de São Paulo (USP) | |
dc.date.accessioned | 2014-05-20T13:49:32Z | |
dc.date.available | 2014-05-20T13:49:32Z | |
dc.date.created | 2014-05-20T13:49:32Z | |
dc.date.issued | 2010-07-01 | |
dc.identifier | Journal of Structural Biology. San Diego: Academic Press Inc. Elsevier B.V., v. 171, n. 1, p. 31-43, 2010. | |
dc.identifier | 1047-8477 | |
dc.identifier | http://hdl.handle.net/11449/17659 | |
dc.identifier | 10.1016/j.jsb.2010.03.019 | |
dc.identifier | WOS:000278836500004 | |
dc.description.abstract | Phospholipases A(2) (Asp49-PLA(2)s) are enzymes responsible for cellular membrane disruption through Ca2+-dependent hydrolysis of phospholipids. A class of these proteins (Lys49-PLA(2)s) does not show catalytic activity but can exert a pronounced local myotoxic effect that is not neutralized by serum therapy. In this work, we present five structures of Lys49-PLA(2)s from snakes of the Bothrops genus in apo form, complexed with PEG molecules and chemically modified by p-bromofenacil bromide (BPB), a classic inhibitor of PLA(2). We present herein an extensive structural analysis including: (i) the function of hydrophobic long-chain molecules as Lys49-PLA(2)s inhibitors, (ii) the role of Lys122, previously indicated as being responsible for Lys49-PLA(2)s catalytic inactivity and, (iii) a structural comparison of the Ca2+-binding loop region between Lys49 and Asp49-PLA(2)s. The Lys122 analysis of 30 different monomers for apo and complexed Lys49-PLA(2)s structures shows that this residue is very flexible and may bind to different carboxyl groups giving stability to the crystal structures. The structural comparisons of the Ca2+-binding loop region between Lys49 and Asp49-PLA(2)s reveal the importance of the Tyr28 residue conservation in Asp49-PLA(2)s to the integrity of this loop. The Tyr28 residue stabilizes this region by an interaction with Gly35 residue. In Lys49-PLA(2)s and low-catalytic Asp49-PLA(2)s this interaction does not occur, preventing the binding of Ca2+. (C) 2010 Elsevier B.V. All rights reserved. | |
dc.language | eng | |
dc.publisher | Academic Press Inc. Elsevier B.V. | |
dc.relation | Journal of Structural Biology | |
dc.relation | 3.433 | |
dc.relation | 3,948 | |
dc.rights | Acesso restrito | |
dc.source | Web of Science | |
dc.subject | Phospholipase A(2) | |
dc.subject | Myotoxicity | |
dc.subject | Homologue phospholipase A(2) (Lys49-PLA(2)s) | |
dc.subject | Ca2+-binding loop | |
dc.subject | X-ray crystallography | |
dc.title | Comparison between apo and complexed structures of bothropstoxin-I reveals the role of Lys122 and Ca2+-binding loop region for the catalytically inactive Lys49-PLA(2)s | |
dc.type | Artículos de revistas | |