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dc.contributor.authordos Santos, Juliana I. [UNESP]
dc.contributor.authorSoares, Andreimar Martins
dc.contributor.authorFontes, Marcos R. M. [UNESP]
dc.date.accessioned2014-05-20T13:49:33Z
dc.date.available2014-05-20T13:49:33Z
dc.date.issued2009-08-01
dc.identifierhttp://dx.doi.org/10.1016/j.jsb.2009.04.003
dc.identifier.citationJournal of Structural Biology. San Diego: Academic Press Inc. Elsevier B.V., v. 167, n. 2, p. 106-116, 2009.
dc.identifier.issn1047-8477
dc.identifier.urihttp://hdl.handle.net/11449/17671
dc.description.abstractPhospholipases A(2) (PLA(2)s) are membrane-associated enzymes that hydrolyze phospholipids at the sn-2 position, releasing lysophospholipids and free fatty acids. Phospholipase A(2) homologues (Lys49-PLA(2)s) are highly myotoxic and cause extensive tissue damage despite not showing measurable catalytic activity. They are found in different snake venoms and represent one third of bothropic venom composition. The importance of these toxins during envenomation is related to the pronounced local myotoxic effect they induce since this effect is not neutralized by serum therapy. We present herein three structures of Lys49-PLA(2)s from Bothrops genus snake venom crystallized under the same conditions, two of which were grown in the presence of alpha-tocopherol (vitamin E). Comparative structural analysis of these and other Lys49-PLA(2)s showed two different patterns of oligomeric conformation that are related to the presence or absence of ligands in the hydrophobic channel. This work also confirms the biological dimer indicated by recent studies in which both C-termini are in the dimeric interface. In this configuration, we propose that the myotoxic site of these toxins is composed by the Lys 20, Lys115 and Arg118 residues. For the first time, a residue from the short-helix (Lys20) is suggested as a member of this site and the importance of Tyr119 residue to myotoxicity of bothropic Lys49-PLA(2)s is also discussed. These results support a complete hypothesis for these PLA(2)s myotoxic activity consistent with all findings on bothropic Lys49-PLA(2)s studied up to this moment, including crystallographic, bioinformatics, biochemical and biophysical data. (C) 2009 Elsevier B.V. All rights reserved.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipLaboratório Nacional de Luz Síncrotron (LNLS)
dc.format.extent106-116
dc.language.isoeng
dc.publisherAcademic Press Inc. Elsevier B.V.
dc.relation.ispartofJournal of Structural Biology
dc.sourceWeb of Science
dc.subjectPhospholipase A(2)en
dc.subjectMyotoxicityen
dc.subjectalpha-Tocopherolen
dc.subjectX-ray crystallographyen
dc.subjectBothrops genusen
dc.subjectHomologue phospholipase A(2) assemblyen
dc.titleComparative structural studies on Lys49-phospholipases A(2) from Bothrops genus reveal their myotoxic siteen
dc.typeArtigo
dcterms.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dcterms.rightsHolderAcademic Press Inc. Elsevier B.V.
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.description.affiliationUNESP, Inst Biociencias, Depto Fis & Biofis, BR-18618000 Botucatu, SP, Brazil
dc.description.affiliationUSP, FCFRP, Depto Anal Clin Toxicol & Bromatol, Ribeirao Preto, SP, Brazil
dc.description.affiliationUnespUNESP, Inst Biociencias, Depto Fis & Biofis, BR-18618000 Botucatu, SP, Brazil
dc.identifier.doi10.1016/j.jsb.2009.04.003
dc.identifier.wosWOS:000268196300002
dc.rights.accessRightsAcesso restrito
unesp.campusUniversidade Estadual Paulista (UNESP), Instituto de Biociências, Botucatupt
unesp.author.orcid0000-0002-4634-6221[3]
dc.relation.ispartofjcr3.433
dc.relation.ispartofsjr3,948
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