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dc.contributor.CRUESPUniversidade Estadual de Campinaspt_BR
dc.typeArtigo de periódicopt_BR
dc.titleStructural bases for a complete myotoxic mechanism: Crystal structures of two non-catalytic phospholipases A(2)-like from Bothrops brazili venompt_BR
dc.contributor.authorFernandes, CAHpt_BR
dc.contributor.authorComparetti, EJpt_BR
dc.contributor.authorBorges, RJpt_BR
dc.contributor.authorHuancahuire-Vega, Spt_BR
dc.contributor.authorPonce-Soto, LApt_BR
dc.contributor.authorMarangoni, Spt_BR
dc.contributor.authorSoares, AMpt_BR
dc.contributor.authorFontes, MRMpt_BR
unicamp.authorFernandes, Carlos A. H. Comparetti, Edson J. Borges, Rafael J. Fontes, Marcos R. M. Univ Estadual Paulista, UNESP, Inst Biociencias, Dep Fis & Biofis, Botucatu, SP, Brazilpt_BR
unicamp.authorHuancahuire-Vega, Salomon Ponce-Soto, Luis Alberto Marangoni, Sergio Univ Estadual Campinas, Inst Biol, Dep Bioquim, Campinas, SP, Brazilpt_BR
unicamp.authorPonce-Soto, Luis Alberto Univ Estadual Campinas, Fac Ciencias Med, Dep Farmacol, Campinas, SP, Brazilpt_BR
unicamp.authorSoares, Andreimar M. Univ Fed Rondonia, FIOCRUZ Rondania, Fundacao Oswaldo Cruz, Porto Velho, RO, Brazilpt_BR
unicamp.authorSoares, Andreimar M. Univ Fed Rondonia, Ctr Estudos Biomol Aplicadas, Porto Velho, RO, Brazilpt_BR
dc.subjectPhospholipase A(2)-likept_BR
dc.subjectMyotoxic mechanismpt_BR
dc.subjectSnake venompt_BR
dc.subjectX-ray crystallographypt_BR
dc.subjectLys49-phospholipase A(2)pt_BR
dc.subjectAmazonian snakept_BR
dc.subject.wosMembrane-damaging Activitiespt_BR
dc.subject.wosPh-induced Dissociationpt_BR
dc.subject.wosC-terminal Regionpt_BR
dc.subject.wosLys(49)-phospholipase A(2)pt_BR
dc.subject.wosLys49-phospholipases A(2)pt_BR
dc.subject.wosSynthetic Peptidespt_BR
dc.description.abstractBothrops brazili is a snake found in the forests of the Amazonian region whose commercial therapeutic antibothropic serum has low efficacy for local myotoxic effects, resulting in an important public health problem in this area. Catalytically inactive phospholipases A(2)-like (Lys49-PLA(2)s) are among the main components from Bothrops genus venoms and are capable of causing drastic myonecrosis. Several studies have shown that the C-terminal region of these toxins, which includes a variable combination of positively charged and hydrophobic residues, is responsible for their activity. In this work we describe the crystal structures of two Lys49-PLA(2)s (BbTX-II and MIX-II) from B. brazili venom and a comprehensive structural comparison with several Lys49-PLA(2)s. Based on these results, two independent sites of interaction were identified between protein and membrane which leads to the proposition of a new myotoxic mechanism for bothropic Lys49-PLA(2)s composed of five different steps. This proposition is able to fully explain the action of these toxins and may be useful to develop efficient inhibitors to complement the conventional antivenom administration. (C) 2013 Elsevier B.V. All rights
dc.relation.ispartofBiochimica Et Biophysica Acta-proteins And Proteomicspt_BR
dc.relation.ispartofabbreviationBBA-Proteins Proteomicspt_BR
dc.publisherElsevier Science Bvpt_BR
dc.identifier.citationBiochimica Et Biophysica Acta-proteins And Proteomics. Elsevier Science Bv, v. 1834, n. 12, n. 2772, n. 2781, 2013.pt_BR
dc.sourceWeb of Sciencept_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.sponsorship1Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorship1Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorship1Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.description.provenanceMade available in DSpace on 2014-08-01T18:29:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2013en
dc.description.provenanceMade available in DSpace on 2015-11-26T17:07:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2013en
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