Serpin-derived peptide substrates for investigating the substrate specificity of human tissue kallikreins hK1 and hK2

Serpin-derived peptide substrates for investigating the substrate specificity of human tissue kallikreins hK1 and hK2

Author Bourgeois, L. Google Scholar
BrillardBourdet, M. Google Scholar
Deperthes, D. Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Tremblay, R. R. Google Scholar
Dube, J. Y. Google Scholar
Gauthier, F. Google Scholar
Institution UNIV TOURS
CHUL
Universidade Federal de São Paulo (UNIFESP)
Abstract The third human tissue kallikrein to be identified, hK2, could be an alternate or complementary marker to kallikrein hK3 (prostate-specific antigen) for prostate diseases, Most of the hK2 in seminal plasma forms an inactive complex with protein C inhibitor (PCI), a serpin secreted by seminal vesicles, As serpin inhibitors behave as suicide substrates that are cleaved early in the interaction with their target enzyme, and kallikreins have different sensitivities to serpin inhibitors, we prepared a series of substrates with intramolecularly quenched fluorescence based on the sequences of the serpin reactive loops, They were used to compare the substrate specificities of hK1 and hK2, which both have trypsin-like specificity, and thus differ from chymotrypsin-like hK3, the serpin-derived peptides behaved as kallikrein substrates whose sensitivities reflected the specificity of the parent inhibitory proteins, Substrates derived from PCI were the most sensitive for both hK1 and hK2 with specificity constants of about 10(7) M-1.s(-1). Those derived from antithrombin III and alpha(2)-antiplasmin were more specific for hK2 while a kallistatin-derived substrate was specifically cleaved by hK1, hK1 and hK2 substrates of greater specificity were obtained using chimeric peptides based on the sequence of serpin reactive loops,The main difference between specificities of hK1 and hK2 arise because hK2 can accommodate positively charged as well as small residues at P-2 and requires an arginyl residue at P-1, Thus, unlike hK1, hK2 does not cleave kininogen derived substrates overlapping the region of N-terminal insertion of bradykinin in human kininogens.
Language English
Date 1997-11-21
Published in Journal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 272, n. 47, p. 29590-29595, 1997.
ISSN 0021-9258 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Biochemistry Molecular Biology Inc
Extent 29590-29595
Origin http://dx.doi.org/10.1074/jbc.272.47.29590
Access rights Open access Open Access
Type Article
Web of Science ID WOS:A1997YG64700033
URI http://repositorio.unifesp.br/handle/11600/25811

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