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

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

Author Andrade, Douglas Autor UNIFESP Google Scholar
Assis, Diego Magno Autor UNIFESP Google Scholar
Santos, Jorge Alexandre Nogueira Autor UNIFESP Google Scholar
Alves, Fabiana Madureira Autor UNIFESP Google Scholar
Hirata, Izaura Yoshico Autor UNIFESP Google Scholar
Araujo, Mariana da Silva Autor UNIFESP Google Scholar
Blaber, Sachiko I. Google Scholar
Blaber, Michael Google Scholar
Juliano, Maria Aparecida Autor UNIFESP Google Scholar
Juliano, Luiz Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Florida State Univ
Abstract KLK13 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.
Keywords Kinin
Kosmotropic salts
Myelin basic protein
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number USPHS/NIH: 1R15NS057771-01
Date 2011-10-01
Published in Biochimie. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 93, n. 10, p. 1701-1709, 2011.
ISSN 0300-9084 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1701-1709
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000295107700009

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