Specificity of human tissue kallikrein towards substrates containing Phe-Phe pair of amino acids

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dc.contributor.author Pimenta, Daniel C.
dc.contributor.author Chao, Julie
dc.contributor.author Chao, Lee
dc.contributor.author Juliano, Maria Aparecida [UNIFESP]
dc.contributor.author Juliano, Luiz [UNIFESP]
dc.date.accessioned 2016-01-24T12:30:48Z
dc.date.available 2016-01-24T12:30:48Z
dc.date.issued 1999-04-15
dc.identifier http://dx.doi.org/10.1042/0264-6021:3390473
dc.identifier.citation Biochemical Journal. London: Portland Press, v. 339, p. 473-479, 1999.
dc.identifier.issn 0264-6021
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/26065
dc.description.abstract We have explored in detail the determinants of specificity for the hydrolysis by human tissue kallikrein (hK(1)) of substrates containing the Phe-Phe amino acid pair, after which hK(1) cleaves kallistatin (human kallikrein-binding protein), a specific serpin for this protease, as well as somatostatin 1-14. Internally quenched fluorogenic peptides were synthesized with the general structure Abz-peptidyl-EDDnp [Abz, o-aminobenzoic acid; EDDnp, N-(2,4-dinitrophenyl)ethylenediamine], based on the natural reactive-centre loop sequence of kallistatin from P-9 to P'(13), and the kinetic parameters of their hydrolysis by hK(1) were determined. All these peptides were cleaved after the Phe-Phe pair. for comparison, we have also examined peptides containing the reactive-centre loop sequences of human protein-C inhibitor (PCI) and rat kallikrein-binding protein, which were hydrolysed after Phe-Arg and Leu-Lys bonds, respectively. Hybrid peptides containing kallistatin-PCI sequences showed that the efficiency of hK(1) activity on the peptides containing kallistatin and PCI sequences depended on both the nature of the P-1 amino acid as well as on residues at the P- and PI-sides. Moreover, we have made systematic modifications on the hydrophobic pair Phe-Phe, and on Lys and lie at the P-3 and P-4 positions according to the peptide substrate, Abz-AIKFFSRQ-EDDnp, All together, we concluded that tissue kallikrein was very effective on short substrates that are cleaved after the Phe-Arg pair; however, hydrolysis after Phe-Phe or other hydrophobic pairs of amino acids was more restrictive, requiring additional enzyme-substrate interaction and/or particular substrate conformations. en
dc.format.extent 473-479
dc.language.iso eng
dc.publisher Portland Press
dc.relation.ispartof Biochemical Journal
dc.rights Acesso aberto
dc.subject fluorescent substrate en
dc.subject kallistatin en
dc.subject peptide en
dc.subject protease en
dc.subject serpin en
dc.title Specificity of human tissue kallikrein towards substrates containing Phe-Phe pair of amino acids en
dc.type Artigo
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Med Univ S Carolina
dc.description.affiliation UNIFESP, Escola Paulista Med, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.description.affiliation Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA
dc.description.affiliationUnifesp UNIFESP, Escola Paulista Med, Dept Biofis, BR-04044020 São Paulo, Brazil
dc.identifier.doi 10.1042/0264-6021:3390473
dc.description.source Web of Science
dc.identifier.wos WOS:000079918400033


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