Snake venom serine proteinases specificity mapping by proteomic identification of cleavage sites

dc.contributor.authorZelanis, Andre
dc.contributor.authorHuesgen, Pitter F.
dc.contributor.authorOliveira, Ana Karina
dc.contributor.authorTashima, Alexandre K. [UNIFESP]
dc.contributor.authorSerrano, Solange M. T.
dc.contributor.authorOverall, Christopher M.
dc.contributor.institutionInst Butantan
dc.contributor.institutionUniv British Columbia
dc.contributor.institutionForschungszentrum Julich
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2018-06-15T18:10:59Z
dc.date.available2018-06-15T18:10:59Z
dc.date.issued2015-01-15
dc.description.abstractMany snake venom toxins are serine proteases but their specific in vivo targets are mostly unknown. Various act on components of the coagulation cascade, and fibrinolytic and kallikrein-kinin systems to trigger various pathological effects observed in the envenomation. Despite showing high similarity in terms of primary structure snake venom serine proteinases (SVSPs) show exquisite specificity towards macromolecular substrates. Therefore, the characterization of their peptide bond specificity is important for understanding the active site preference associated with effective proteolysis as well as for the design of peptide substrates and inhibitors. Bothrops jararaca contains various SVSPs among which Bothrops protease A is a specific fibrinogenolytic agent and PA-BJ is a platelet-activating enzyme. In this study we used proteome derived peptide libraries in the Proteomic Identification of protease Cleavage Sites (PICS) approach to explore the peptide bond specificity of Bothrops protease A and PA-BJ in order to determine their individual peptide cleavage sequences. A total of 371 cleavage sites (208 for Bothrops protease A and 163 for PA-BJ) were detected and both proteinases displayed a clear preference for arginine at the P1 position. Moreover, the analysis of the specificity profiles of Bothrops protease A and PA-BJ revealed subtle differences in the preferences along P6-P6 ', despite a common yet unusual preference for Pro at P2. Taken together, these results map the subsite specificity of both SVSPs and shed light in the functional differences between these proteinases.Biological significanceProteolysis is key to various pathological effects observed upon envenomation by viperid snakes. The use of the Proteomic Identification of protease Cleavage Sites (PICS) approach for the easy mapping of proteinase subsite preferences at both the prime- and non-prime sides concurrently gives rise to a fresh understanding of the interaction of the snake venom senile proteinases with peptide and macromolecular substrates and indicates that their hydrolytic activity is influenced by the amino acid sequences adjacent to the scissile bond. (C) 2014 Elsevier B.V. All rights reserved.en
dc.description.affiliationInst Butantan, Lab Especial Toxinol Aplicada, Ctr Toxins Immuneresponse & Cell Signaling CeTICS, BR-05503000 Sao Paulo, Brazil
dc.description.affiliationUniv British Columbia, Ctr Blood Res, Vancouver, BC V5Z 1M9, Canada
dc.description.affiliationUniv British Columbia, Dept Oral Biol & Med Sci, Vancouver, BC V5Z 1M9, Canada
dc.description.affiliationForschungszentrum Julich, Cent Inst Engn Elect & Analyt ZEA 3, D-52425 Julich, Germany
dc.description.affiliationUniv Sao Paulo, Dept Bioquim, Inst Quim, BR-05508 Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, Brazil
dc.description.affiliationUniv British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Bioquim, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipGerman Academic Exchange Service (DAAD)
dc.description.sponsorshipMichael Smith Foundation for Health Research (MSFHR)
dc.description.sponsorshipCIHR
dc.description.sponsorshipCanada Foundations for Innovation
dc.description.sponsorshipIDFAPESP: 2010/17328-0
dc.description.sponsorshipIDFAPESP: 2011/08514-8
dc.description.sponsorshipIDFAPESP: 2011/23403-8
dc.description.sponsorshipIDFAPESP: 2013/07467-1
dc.description.sponsorshipIDCIHR: MOP-111-055
dc.format.extent260-267
dc.identifierhttp://dx.doi.org/10.1016/j.jprot.2014.10.002
dc.identifier.citationJournal Of Proteomics. Amsterdam: Elsevier Science Bv, v. 113, p. 260-267, 2015.
dc.identifier.doi10.1016/j.jprot.2014.10.002
dc.identifier.issn1874-3919
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/44589
dc.identifier.wosWOS:000347582200018
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofJournal Of Proteomics
dc.rightsAcesso restrito
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectSnake venomen
dc.subjectSerine proteinaseen
dc.subjectProteomic Identification of proteaseen
dc.subjectCleavage Sitesen
dc.subjectPeptide bond specificityen
dc.subjectProteome derived peptide libraryen
dc.titleSnake venom serine proteinases specificity mapping by proteomic identification of cleavage sitesen
dc.typeArtigo
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