S(1)' and S(2)' subsite specificities of human plasma kallikrein and tissue kallikrein 1 for the hydrolysis of peptides derived from the bradykinin domain of human kininogen

S(1)' and S(2)' subsite specificities of human plasma kallikrein and tissue kallikrein 1 for the hydrolysis of peptides derived from the bradykinin domain of human kininogen

Author Lima, Aurelio Resende Autor UNIFESP Google Scholar
Alves, Fabiana M. Autor UNIFESP Google Scholar
Angelo, Pedro Francisco Autor UNIFESP Google Scholar
Andrade, Douglas Autor UNIFESP Google Scholar
Blaber, Sachiko I. Google Scholar
Blaber, Michael Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Florida State Univ
Abstract The S(1)' and S(2)' subsite specificities of human tissue kallikrein 1 (KLK1) and human plasma kallikrein (HPK) were examined with the peptide series Abz-GFSPFRXSRIQ-EDDnp and Abz-GFSPFRSXRIQ-EDDnp [X=natural amino acids or S( PO 3 H 2) x. KLK1 efficiently hydrolyzed most of the peptides except those containing negatively charged amino acids at P 19 and P 29 positions. Abz-GFSPFRSSRIQ-EDDnp, as in human kininogen, is the best substrate for KLK1 and exclusively cleaved the R-S bond. All other peptides were cleaved also at the F-R bond. the synthetic human kininogen segment Abz-MISLMKRPPGFSPFRS(390)S(391)RI-NH(2) was hydrolyzed by KLK1 first at R-S and then at M-K bonds, releasing Lys-bradykinin. in the S(390) and S(391) phosphorylated analogs, this order of hydrolysis was inverted due to the higher resistance of the R-S bond. Abz-MISLMKRPPGFSPFRSS(PO(3)H(2))(391)RI-NH(2) was hydrolyzed by KLK1 at M-K and mainly at the F-R bond, releasing des-(Arg(9))-Lys-Bk which is a B1 receptor agonist. HPK cleaved all the peptides at R and showed restricted specificity for S in the S(1)' subsite, with lower specificity for the S(2)' subsite. Abz-MISLMKRPPGFSPFRSSRI-NH(2) was efficiently hydrolyzed by HPK under bradykinin release, while the analogs containing S(PO(3)H(2)) were poorly hydrolyzed. in conclusion, S(1)' and S(2)' subsite specificities of KLK1 and HPK showed peculiarities that were observed with substrates containing the amino acid sequence of human kininogen.
Keywords bradykinin
kinin
peptidase
peptides
phosphorylation
protease
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2008-12-01
Published in Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 389, n. 12, p. 1487-1494, 2008.
ISSN 1431-6730 (Sherpa/Romeo, impact factor)
Publisher Walter de Gruyter & Co
Extent 1487-1494
Origin http://dx.doi.org/10.1515/BC.2008.166
Access rights Closed access
Type Article
Web of Science ID WOS:000262137600005
URI http://repositorio.unifesp.br/handle/11600/31095

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