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Substrate specificity and inhibition of human kallikrein-related peptidase 3 (KLK3 or PSA) activated with sodium citrate and glycosaminoglycans

Authors
  • Andrade, Douglas
  • Assis, Diego M.
  • Lima, Aurelio Resende
  • Oliveira, Juliana R.
  • Araujo, Mariana S.
  • Blaber, Sachiko I.
  • Blaber, Michael
  • Juliano, Maria A.
  • Juliano, Luiz
Type
Published Article
Journal
Archives of Biochemistry and Biophysics
Publisher
Elsevier BV
Publication Date
Jan 01, 2010
Volume
498
Issue
1
Pages
74–82
Identifiers
DOI: 10.1016/j.abb.2010.03.022
Source
Elsevier
Keywords
License
Unknown

Abstract

We report the enzymatic properties and substrate specificity of human recombinant KLK3 in the presence of glycosaminoglycans (GAGs) and sodium citrate. This salt is highly concentrated in prostate and in its presence KLK3 had a similar hydrolytic efficiency as chymotrypsin. In contrast to the latter peptidase, KLK3 activated by sodium citrate efficiently hydrolyzed substrates containing R, H and P at the P1 position. Activated KLK3 also cleaved peptides derived from the bradykinin domain of human kininogen at the same sites as human kallikrein KLK1, but presented low kininogenase activity. Angiotensin I has several sites for hydrolysis by KLK3; however, it was cleaved only at the Y–I bond (DRVY↓IHPFHL). Sodium citrate modulated KLK3 conformation as observed by alterations to the intrinsic fluorescence of phenylalanines and tryptophans. Activated KLK3 was reversibly inhibited by Z-Pro-Prolinal and competitively inhibited by ortho-phenantroline. Together, these are noteworthy observations for the future design of specific non-peptide inhibitors of KLK3 and to find natural substrates.

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