Inhibition of phosphoglycerate kinase by salicylates.

A kinetic analysis has been performed on the inhibition of the yeast phosphoglycerate kinase (APT:3-phospho-D-glycerate 1-phosphotransferase, EC 2.7.2.3) reaction by 2-hydroxybenzoate (salicylate) and two of its iododerivatives, 2-hydroxy-5-iodobenzoate and 2-hydroxy-3,5-diiodobenzoate. The results give evidence that the salicylates mimic the nucleotide binding at the catalytic centre. The enzyme has an affinity for salicylate that dramatically increases for each iodine atom introduced to the benzene ring. Parabolic inhibition give evidence for two inhibitor binding sites per enzyme molecule. The two Ki values are 10 and 180 mM for salicylate, 0.60 and 13 mM for iodosalicylate and 0.064 and 0.70 mM for diiodosalicylate. The 2'-OH of the nucleotide substrate appears to be important for the catalytic events.