Functional tyrosine residue in the active center of human dipeptidyl peptidase III.

Abstract

Abstract Human dipeptidyl peptidase III (DPP III) is a member of the metallopeptidase family M49 with an implied role in the pain-modulatory system and endogenous defense against oxidative stress. Here, we report the heterologous expression of human DPP III and the site-directed mutagenesis results which demonstrate a functional role for Tyr318 at the active site of this enzyme. The substitution of Tyr318 to Phe decreased kcat by two orders of magnitude without altering the binding affinity of substrate, or of a competitive hydroxamate inhibitor designed to interact with S1 and S2 subsites. The results indicate that the conserved tyrosine could be involved in transition state stabilization during the catalytic action of M49 peptidases.

• Authors: Branka Salopek-Sondi, Bojana Vukelić, Jasminka Spoljarić, Sumski Simaga, Dusica Vujaklija, Janja Makarević, Nina Jajcanin, Marija Abramić
• Journal: Biological chemistry (Biol Chem) Vol. 389 Issue 2 Pg. 163-7 (Feb 2008) ISSN: 1431-6730 [Print] Germany
• PMID: 18163885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tyrosine
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
• dipeptidyl peptidase III

Topics

• Binding Sites
• Catalysis
• Dipeptidyl-Peptidases and Tripeptidyl-Peptidases (chemistry, metabolism)
• Humans
• Kinetics
• Mutagenesis, Site-Directed
• Tyrosine