Effect of zinc and calcium ions on the rat kidney membrane-bound form of dipeptidyl peptidase IV.
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Date
2013-09
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Abstract
Dipeptidyl peptidase IV (DPP-IV) is an ectopeptidase with many roles, and a target of therapies for different
pathologies. Zinc and calcium produce mixed inhibition of porcine DPP-IV activity. To investigate whether these
results may be generalized to mammalian DPP-IV orthologues, we purified the intact membrane-bound form from rat
kidney. Rat DPP-IV hydrolysed Gly-Pro-p-nitroanilide with an average Vmax of 0.86±0.01 μmol min–1mL–1 and KM
of 76±6 μM. The enzyme was inhibited by the DPP-IV family inhibitor L-threo-Ile-thiazolidide (Ki=64.0±0.53 nM),
competitively inhibited by bacitracin (Ki=0.16±0.01 mM) and bestatin (Ki=0.23±0.02 mM), and irreversibly inhibited
by TLCK (IC50 value of 1.20±0.11 mM). The enzyme was also inhibited by divalent ions like Zn2+ and Ca2+, for
which a mixed inhibition mechanism was observed (Ki values of the competitive component: 0.15±0.01 mM and
50.0±1.05 mM, respectively). According to bioinformatic tools, Ca2+ ions preferentially bound to the β-propeller
domain of the rat and human enzymes, while Zn2+ ions to the α-β hydrolase domain; the binding sites were essentially
the same that were previously reported for the porcine DPP-IV. These data suggest that the cationic susceptibility of
mammalian DPP-IV orthologues involves conserved mechanisms.
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Keywords
Binding site prediction, cancer, diabetes, dipeptidyl peptidase IV, divalent cations, inhibition
Citation
Gòmez Hansel, Chappè Mae, Valiente Pedroa, Pons Tirso, Chàvez Marìa de Los Angeles, Charli Jean-Louis, Pascual Isel. Effect of zinc and calcium ions on the rat kidney membrane-bound form of dipeptidyl peptidase IV. Journal of Biosciences. 2013 Sept; 38(3): 461-469.