Structural bases for a complete myotoxic mechanism: Crystal structures of two non-catalytic phospholipases A(2)-like from Bothrops brazili venom

dc.creatorFernandes, CAH
dc.creatorComparetti, EJ
dc.creatorBorges, RJ
dc.creatorHuancahuire-Vega, S
dc.creatorPonce-Soto, LA
dc.creatorMarangoni, S
dc.creatorSoares, AM
dc.creatorFontes, MRM
dc.date2013
dc.dateDEC
dc.date2014-08-01T18:29:30Z
dc.date2015-11-26T17:07:58Z
dc.date2014-08-01T18:29:30Z
dc.date2015-11-26T17:07:58Z
dc.date.accessioned2018-03-28T23:56:32Z
dc.date.available2018-03-28T23:56:32Z
dc.identifierBiochimica Et Biophysica Acta-proteins And Proteomics. Elsevier Science Bv, v. 1834, n. 12, n. 2772, n. 2781, 2013.
dc.identifier1570-9639
dc.identifier0006-3002
dc.identifierWOS:000329418300035
dc.identifier10.1016/j.bbapap.2013.10.009
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/79687
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/79687
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1280230
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionBothrops 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 reserved.
dc.description1834
dc.description12
dc.description2772
dc.description2781
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.languageen
dc.publisherElsevier Science Bv
dc.publisherAmsterdam
dc.publisherHolanda
dc.relationBiochimica Et Biophysica Acta-proteins And Proteomics
dc.relationBBA-Proteins Proteomics
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectPhospholipase A(2)-like
dc.subjectMyotoxic mechanism
dc.subjectSnake venom
dc.subjectX-ray crystallography
dc.subjectLys49-phospholipase A(2)
dc.subjectAmazonian snake
dc.subjectMembrane-damaging Activities
dc.subjectPh-induced Dissociation
dc.subjectC-terminal Region
dc.subjectSnake-venom
dc.subjectLys(49)-phospholipase A(2)
dc.subjectLys49-phospholipases A(2)
dc.subjectSynthetic Peptides
dc.subjectAmino-acids
dc.subjectLys49
dc.subjectInsights
dc.titleStructural bases for a complete myotoxic mechanism: Crystal structures of two non-catalytic phospholipases A(2)-like from Bothrops brazili venom
dc.typeArtículos de revistas


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