P-I class metalloproteinase from Bothrops moojeni venom is a post-proline cleaving peptidase with kininogenase activity: Insights into substrate selectivity and kinetic behavior

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dc.contributor.authorOkamoto, Debora Noma [UNIFESP]
dc.contributor.authorKondo, Marcia Yuri [UNIFESP]
dc.contributor.authorOliveira, Lilian Caroline Gonçalves de [UNIFESP]
dc.contributor.authorHonorato, Rodrigo Vargas
dc.contributor.authorZanphorlin, Letícia Maria
dc.contributor.authorCoronado, Monika Aparecida
dc.contributor.authorAraujo, Mariana Silva [UNIFESP]
dc.contributor.authorMotta, Guacyara da [UNIFESP]
dc.contributor.authorVeronez, Camila Lopes [UNIFESP]
dc.contributor.authorAndrade, Sheila Siqueira [UNIFESP]
dc.contributor.authorOliveira, Paulo Sergio Lopes de
dc.contributor.authorArni, Raghuvir Krishnaswamy
dc.contributor.authorCintra, Adélia Cristina Oliveira de
dc.contributor.authorSampaio, Suely Vilela
dc.contributor.authorJuliano, Maria Aparecida [UNIFESP]
dc.contributor.authorJuliano, Luiz [UNIFESP]
dc.contributor.authorMurakami, Mario Tyago
dc.contributor.authorGouvea, Iuri Estrada [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionCtr Nacl Pesquisas Energia & Mat
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUNESP
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.date.accessioned2016-01-24T14:35:20Z
dc.date.available2016-01-24T14:35:20Z
dc.date.issued2014-03-01
dc.description.abstractSnake venom metalloproteinases (SVMPs) belonging to P-I class are able to hydrolyze extracellular matrix proteins and coagulation factors triggering local and systemic reactions by multiple molecular mechanisms that are not fully understood. BmooMP alpha-I, a P-I class SMVP from Bothrops moojeni venom, was active upon neuro- and vaso-active peptides including angiotensin I, bradykinin, neurotensin, oxytocin and substance P. Interestingly, BmooMPa-I showed a strong bias towards hydrolysis after proline residues, which is unusual for most of characterized peptidases. Moreover, the enzyme showed kininogenase activity similar to that observed in plasma and cells by kallikrein. FRET peptide assays indicated a relative promiscuity at its S-2-S '(2) subsites, with proline determining the scissile bond. This unusual post-proline cleaving activity was confirmed by the efficient hydrolysis of the synthetic combinatorial library MCA-GXXPXXQ-EDDnp, described as resistant for canonical peptidases, only after Pro residues. Structural analysis of the tripeptide LPL complexed with BmooMP alpha-I, generated by molecular dynamics simulations, assisted in defining the subsites and provided the structural basis for subsite preferences such as the restriction of basic residues at the S-2 subsite due to repulsive electrostatic effects and the steric impediment for large aliphatic or aromatic side chains at the Si subsite. These new functional and structural findings provided a further understanding of the molecular mechanisms governing the physiological effects of this important class of enzymes in envenomation process. (c) 2014 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliationCtr Nacl Pesquisas Energia & Mat, Lab Nacl Biociencias, BR-13083100 Campinas, SP, Brazil
dc.description.affiliationUniv Estadual Campinas, Inst Quim, Dept Organ, BR-13083970 Campinas, SP, Brazil
dc.description.affiliationUNESP, Dept Fis, IBILCE, BR-15054000 Sao Jose Do Rio Preto, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Ginecol, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, BR-14040903 Ribeirao Preto, SP, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Bioquim, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Ginecol, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDFAPESP: 2012/50191-4
dc.format.extent545-552
dc.identifierhttp://dx.doi.org/10.1016/j.bbapap.2013.12.014
dc.identifier.citationBiochimica Et Biophysica Acta-proteins and Proteomics. Amsterdam: Elsevier B.V., v. 1844, n. 3, p. 545-552, 2014.
dc.identifier.doi10.1016/j.bbapap.2013.12.014
dc.identifier.fileWOS000333491100008.pdf
dc.identifier.issn1570-9639
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/37451
dc.identifier.wosWOS:000333491100008
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBiochimica Et Biophysica Acta-proteins and Proteomics
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectSnake venom metalloproteinaseen
dc.subjectKininogenase activityen
dc.subjectFRET peptidesen
dc.subjectSubstrate specificityen
dc.subjectMolecular dynamics simulationsen
dc.titleP-I class metalloproteinase from Bothrops moojeni venom is a post-proline cleaving peptidase with kininogenase activity: Insights into substrate selectivity and kinetic behavioren
dc.typeinfo:eu-repo/semantics/article
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