Activity of human kallikrein-related peptidase 6 (KLK6) on substrates containing sequences of basic amino acids. Is it a processing protease?

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dc.citation.issue5
dc.citation.volume1865
dc.contributor.authorSilva, Roberta N. [UNIFESP]
dc.contributor.authorOliveira, Lilian C. G. [UNIFESP]
dc.contributor.authorParise, Carolina B. [UNIFESP]
dc.contributor.authorOliveira, Juliana R. [UNIFESP]
dc.contributor.authorSeverino, Beatrice
dc.contributor.authorCorvino, Angela
dc.contributor.authordi Vaio, Paola
dc.contributor.authorTemussi, Piero A.
dc.contributor.authorCaliendo, Giuseppe
dc.contributor.authorSantagada, Vincenzo
dc.contributor.authorJuliano, Luiz [UNIFESP]
dc.contributor.authorJuliano, Maria A. [UNIFESP]
dc.coverageAmsterdam
dc.date.accessioned2020-07-13T11:53:25Z
dc.date.available2020-07-13T11:53:25Z
dc.date.issued2017
dc.description.abstractHuman kallikrein 6 (KLK6) is highly expressed in the central nervous system and with elevated level in demyelinating disease. KLK6 has a very restricted specificity for arginine (R) and hydrolyses myelin basic protein, protein activator receptors and human ionotropic glutamate receptor subunits. Here we report a previously unreported activity of KLK6 on peptides containing clusters of basic amino acids, as in synthetic fluorogenic peptidyl-Arg-7-amino-4-carbamoylmethylcoumarin (peptidyl-ACC) peptides and FRET peptides in the format of Abz-peptidyl-Q-EDDnp (where Abz = ortho-aminobenzoic acid and Q-EDDnp = glutaminyl-N-(2,4dinitrophenyl) ethylenediamine), in which pairs or sequences of basic amino acids (R or K) were introduced. Surprisingly, KLK6 hydrolyzed the fluorogenic peptides Bz-A-R down arrow R-ACC and Z-R down arrow R-MCA between the two R groups, resulting in non-fluorescent products. FRET peptides containing furin processing sequences of human MMP-14, nerve growth factor (NGF), Neurotrophin-3 (NT-3) and Neurotrophin-4 (NT-4) were cleaved by KLK6 at the same position expected by furin. Finally, KLK6 cleaved FRET peptides derived from human proenkephalin after the KR, the more frequent basic residues flanking enkephalins in human proenkephalin sequence. This result suggests the ability of KLK6 to release enkephalin from proenkephalin precursors and resembles furin a canonical processing proteolytic enzyme. Molecular models of peptides were built into the KLK6 structure and the marked preference of the cut between the two R of the examined peptides was related to the extended conformation of the substrates. (C) 2017 Elsevier B.V. All rights reserved.en
dc.description.affiliationUniv Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Rua Tres de Maio 100, BR-04044020 Sao Paulo, Brazil
dc.description.affiliationUniv Naples Federico II, Dipartimento Farm, Via D Montesano 49, I-80131 Naples, Italy
dc.description.affiliationKings Coll London, Wohl Inst, 5 Cutcombe Rd, London SE5 9RT, England
dc.description.affiliationUniv Naples Federico II, Dipartimento Sci Chim, Comp Univ Monte St Angelo Via Cintia 21, I-80126 Naples, Italy
dc.description.affiliationUnifespUniv Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Rua Tres de Maio 100, BR-04044020 Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.description.sponsorshipInstituto Nacional de Fluidos Complexos (INCT-FCx)
dc.description.sponsorshipIDFAPESP: 12/50191-4R
dc.description.sponsorshipIDCNPq: 471340/2011-1
dc.description.sponsorshipIDCNPq: 470388/2010-2
dc.description.sponsorshipIDINCT-FCx: 573560/2008-0
dc.format.extent558-564
dc.identifierhttp://dx.doi.org/10.1016/j.bbapap.2017.02.017
dc.identifier.citationBiochimica Et Biophysica Acta-Proteins And Proteomics. Amsterdam, v. 1865, n. 5, p. 558-564, 2017.
dc.identifier.doi10.1016/j.bbapap.2017.02.017
dc.identifier.issn1570-9639
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54609
dc.identifier.wosWOS:000400714800011
dc.language.isoeng
dc.publisherElsevier Science Bv
dc.relation.ispartofBiochimica Et Biophysica Acta-Proteins And Proteomics
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectProteolytic enzymesen
dc.subjectPlasma kallikreinen
dc.subjectTissue kallikreinen
dc.subjectNeurotrophinsen
dc.subjectMatrix metalloproteasesen
dc.subjectEnkephalinsen
dc.titleActivity of human kallikrein-related peptidase 6 (KLK6) on substrates containing sequences of basic amino acids. Is it a processing protease?en
dc.typeinfo:eu-repo/semantics/article
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