Substrate specificity of kallikrein-related peptidase 13 activated by salts or glycosaminoglycans and a search for natural substrate candidates

dc.contributor.authorAndrade, Douglas [UNIFESP]
dc.contributor.authorAssis, Diego Magno [UNIFESP]
dc.contributor.authorSantos, Jorge Alexandre Nogueira [UNIFESP]
dc.contributor.authorAlves, Fabiana Madureira [UNIFESP]
dc.contributor.authorHirata, Izaura Yoshico [UNIFESP]
dc.contributor.authorAraujo, Mariana da Silva [UNIFESP]
dc.contributor.authorBlaber, Sachiko I.
dc.contributor.authorBlaber, Michael
dc.contributor.authorJuliano, Maria Aparecida [UNIFESP]
dc.contributor.authorJuliano, Luiz [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionFlorida State Univ
dc.date.accessioned2016-01-24T14:17:14Z
dc.date.available2016-01-24T14:17:14Z
dc.date.issued2011-10-01
dc.description.abstractKLK13 is a kallikrein-related peptidase preferentially expressed in tonsils, esophagus, testis, salivary glands and cervix. We report the activation of KLK13 by kosmotropic salts and glycosaminoglycans and its substrate specificity by employing a series of five substrates derived from the fluorescence resonance energy transfer (FRET) peptide Abz-KLRSSKQ-EDDnp. KLK13 hydrolyzed all these peptides only at basic residues with highest efficiency for R; furthermore, the S(3) to S(2)' subsites accepted most of the natural amino acids with preference also for basic residues. Using a support-bound FRET peptide library eight peptide substrates were identified containing sequences of proteins found in testis and one with myelin basic protein sequence, each of which was well hydrolyzed by KLK13. Histatins are salivary peptides present in higher primates with broad antifungal and mucosal healing activities that are generated from the hydrolysis from large precursor peptides. KLK13 efficiently hydrolyzed synthetic histatin 3 exclusively at R(25) (DSHAKRHHGYKRKFHEKHHSHRGYR(25)down arrow SNYLYDN) that is the first cleavage observed inside the salivary gland.In conclusion, the observed hydrolytic activities of KLK13 and its co-localization with its activators, glycosaminoglycans in the salivary gland and high concentration of sodium citrate in male reproductive tissues, indicates that KLK13 may play a role in the defense of the upper digestive apparatus and in male reproductive organs. (C) 2011 Elsevier Masson SAS. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biochem, BR-0404420 São Paulo, Brazil
dc.description.affiliationFlorida State Univ, Coll Med, Dept Biomed Sci, Tallahassee, FL 32306 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04044020 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biochem, BR-0404420 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipUSPHS/NIH
dc.description.sponsorshipIDUSPHS/NIH: 1R15NS057771-01
dc.format.extent1701-1709
dc.identifierhttp://dx.doi.org/10.1016/j.biochi.2011.05.037
dc.identifier.citationBiochimie. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 93, n. 10, p. 1701-1709, 2011.
dc.identifier.doi10.1016/j.biochi.2011.05.037
dc.identifier.fileWOS000295107700009.pdf
dc.identifier.issn0300-9084
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34066
dc.identifier.wosWOS:000295107700009
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofBiochimie
dc.rightsAcesso aberto
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectKininen
dc.subjectProteaseen
dc.subjectHistatinsen
dc.subjectKosmotropic saltsen
dc.subjectMyelin basic proteinen
dc.titleSubstrate specificity of kallikrein-related peptidase 13 activated by salts or glycosaminoglycans and a search for natural substrate candidatesen
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