Characterization and comparative 3D modeling of CmPI-II, a novel 'non-classical' Kazal-type inhibitor from the marine snail Cenchritis muricatus (Mollusca)

dc.contributor.authorGonzalez, Yamile
dc.contributor.authorPons, Tirso
dc.contributor.authorGil, Jeovanis
dc.contributor.authorBesada, Vladimir
dc.contributor.authorAlonso-del-Rivero, Maday
dc.contributor.authorTanaka, Aparecida S.
dc.contributor.authorAraujo, Mariana S.
dc.contributor.authorChavez, Maria A.
dc.contributor.institutionUniv La Habana
dc.contributor.institutionCentro de Ingenieria Genetica y Biotecnologia
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T13:49:12Z
dc.date.available2016-01-24T13:49:12Z
dc.date.issued2007-11-01
dc.description.abstractThe complete amino acid sequence obtained by electrospray ionization tandem mass spectrometry of the proteinase inhibitor CmPI-II isolated from Cenchritis muricatus is described. CmPI-II is a 5480-Da protein with three disulfide bridges that inhibits human neutrophil elastase (HNE) (K-i 2.6 +/- 0.2 nM), trypsin (K-i 1.1 +/- 0.9 nM), and other serine proteinases such as subtilisin A (K-i 30.8 +/- 1.2 nm) and pancreatic elastase (K-i 145.0 +/- 4.4 nM); chymotrypsin, pancreatic and plasma kallikreins, thrombin and papain are not inhibited. CmPI-II shares homology with the Kazal-type domain and may define a new group of 'non-classical' Kazal inhibitors according to its Cys(I)-Cys(v) disulfide bridge position. the 3D model of CmPI-II exhibits similar secondary structure characteristics to Kazal-type inhibitors and concurs with circular dichroism experiments. A 3D model of the CmPI-II/HNE complex provides a structural framework for the interpretation of its experimentally determined Ki value. the model shows both similar and different contacts at the primary binding sites in comparison with the structure of turkey ovomucoid third domain (OMTKY3)/HNE used as template. Additional contacts calculated at the protease-inhibitor interface could also contribute to the association energy of the complex. This inhibitor represents an exception in terms of specificity owing to its ability to strongly inhibit elastases and trypsin.en
dc.description.affiliationUniv La Habana, Fac Biol, Centro de Estudios de Protreinas, Havana 10400, Cuba
dc.description.affiliationCentro de Ingenieria Genetica y Biotecnologia, Havana 10600, Cuba
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biochem, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biochem, BR-04044020 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent1183-1194
dc.identifierhttp://dx.doi.org/10.1515/BC.2007.129
dc.identifier.citationBiological Chemistry. Berlin: Walter de Gruyter & Co, v. 388, n. 11, p. 1183-1194, 2007.
dc.identifier.doi10.1515/BC.2007.129
dc.identifier.issn1431-6730
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30145
dc.identifier.wosWOS:000250905900009
dc.language.isoeng
dc.publisherWalter de Gruyter & Co
dc.relation.ispartofBiological Chemistry
dc.rightsAcesso restrito
dc.subjecthuman neutrophil elastaseen
dc.subjectmarine invertebrateen
dc.subjectporcine pancreatic elastaseen
dc.subjectserine proteinase inhibitoren
dc.subjectsubtilisinen
dc.subjecttrypsinen
dc.titleCharacterization and comparative 3D modeling of CmPI-II, a novel 'non-classical' Kazal-type inhibitor from the marine snail Cenchritis muricatus (Mollusca)en
dc.typeArtigo
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