Differences in substrate and inhibitor sequence specificity of human, mouse and rat tissue kallikreins

Página do item simplificado
dc.contributor.authorFogaça, Sandro E. [UNIFESP]
dc.contributor.authorMelo, Robson L. [UNIFESP]
dc.contributor.authorPimenta, Daniel C. [UNIFESP]
dc.contributor.authorHosoi, Kazuo
dc.contributor.authorJuliano, Luiz [UNIFESP]
dc.contributor.authorJuliano, Maria Aparecida [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Tokushima
dc.date.accessioned2016-01-24T12:37:12Z
dc.date.available2016-01-24T12:37:12Z
dc.date.issued2004-06-15
dc.description.abstractThe kininogenase activities of mouse (mK1), rat (rK1) and human (hK1) tissue kallikrems were assayed with the bradykinin-containing synthetic peptides NH2-MTEMARRPPGFSPFRSVTVQ-NH2 (where Abz stands for o-aminobenzoyl) and Abz-MTS-VIRRPPGFSPFRAPRV-NH2, which correspond to fragments Met(374)-Gln(393) and Met(375)-Val(393) of mouse and rat LMWKs (low-molecular-mass kininogens) with the addition of Abz. Bradykinin was released from these peptides by the mK1- and rK1-mediated hydrolysis of Arg-Arg and Arg-Ser (or Arg-Ala) peptide bonds. However, owing to preferential hydrolysis of Phe-Arg compared with the Arg-Ala bond in the peptide derived from rat LMWK, hK1 released bradykinin only from the mouse LMWK fragment and preferentially released des-[Arg(9)]bradykinin from the rat LMWK fragment (Abz-MTSVIRRPPGFSPFRAPRV-NH2). the formation of these hydrolysis products was examined in more detail by determining the kinetic parameters for the hydrolysis of synthetic, internally quenched fluorescent peptides containing six N- or C-terminal amino acids of bradykinin added to the five downstream or upstream residues of mouse and rat kininogens respectively. One of these peptides, Abz-GFSPFRAPRVQ-EDDnp (where EDDnp stands for ethylenediamine 2,4-dinitrophenyl), was preferentially hydrolysed at the Phe-Arg bond, confirming the potential des-[Arg(9)]bradykinin-releasing activity of hK1 on rat kininogen. the proline residue that is two residues upstream of bradykinin in rat kininogen is, in part, responsible for this pattern of hydrolysis, since the peptide Abz-GFSPFRASRVQ-EDDnp was preferentially cleaved at the Arg-Ala bond by hK1. Since this peptidase accepts the arginine or phenylalanine residue at its S-1 subsite, this preference seems to be determined by the prime site of the substrates. These findings also suggested that the effects observed in rats overexpressing hK1 should consider the activation of B1 receptors by des-[Arg(9)] bradykinin. for further comparison, two short internally quenched fluorescent peptides that bind to hK1 with affinity in the nM range and some inhibitors described previously for hK1 were also assayed with mK1 and rK1.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-0404420 São Paulo, Brazil
dc.description.affiliationUniv Tokushima, Sch Dent, Dept Physiol & Oral Physiol, Tokushima 7708504, Japan
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-0404420 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent775-781
dc.identifierhttp://dx.doi.org/10.1042/BJ20031047
dc.identifier.citationBiochemical Journal. London: Portland Press, v. 380, p. 775-781, 2004.
dc.identifier.doi10.1042/BJ20031047
dc.identifier.issn0264-6021
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/27793
dc.identifier.wosWOS:000222338100021
dc.language.isoeng
dc.publisherPortland Press
dc.relation.ispartofBiochemical Journal
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectbradykininen
dc.subjectfluorescent peptideen
dc.subjectinflammationen
dc.subjectinhibitoren
dc.subjectkallikreinen
dc.subjectproteaseen
dc.titleDifferences in substrate and inhibitor sequence specificity of human, mouse and rat tissue kallikreinsen
dc.typeinfo:eu-repo/semantics/article
Arquivos
Coleções
EPM - Artigos