engleski

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

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. Apart from active site-zinc ligation, many details of the DPP III (M49 peptidase) mechanism are unknown. We report heterologous expression of human DPP III and the site-directed mutagenesis results which demonstrate a functional role for Tyr318 at this enzyme's active site . 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 favor the involvement of the conserved tyrosine in transition state stabilization during the catalytic action of M49 peptidases. References: Salopek-Sondi, B., Vukelić, B., Špoljarić, J., Šimaga, Š., Vujaklija, D., Makarević, J., Jajčanin, N., Abramić, M. (2008): Functional tyrosine residue in the active center of human dipeptidyl peptidase III, Biol. Chem. 389: 163-167.

Dipeptidyl peptidase III; Metallopeptidase; Tyr318

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