Inhibition of Phosphoglycerate Kinase by Products and Product Homologues

This paper gives a presentation of ADP and AMP inhibition of phosphoglycerate kinase with MgATP 2− and 3‐phospho‐ d ‐glycerate as substrates at high and low Mg 2+ concentrations and pH 7.8. The enzyme seems to contain at least two nucleotide binding sites, one presumably binding to MgATP 2− and the other to ADP 3− . The ADP 3− binding site might bind MgADP 1− also. AMP 2− competes for the same form of the enzyme, probably the same site, as MgATP 2− . ADP 3− and MgADP 1− are competive inhibitors and AMP 2− is a non‐competitive inhibitor of 3‐ P ‐glycerate. Values of the inhibition constant, K i , for ADP 3− at low Mg 2+ level and MgADP 1− at high Mg 2+ level are 0.2 and 0.02 mM, respectively. The latter value is about ten times less than the expected Michaelis constant for corresponding substrate in the reverse reaction. K i for AMP is about 2.0 mM at both low and high Mg 2+ concentrations but the inhibition is stronger at a high than at a low Mg 2+ level, probably caused by conformational and/or other differences of the enzyme at these two metal ion concentrations. The main catalytic reaction suits a pattern that is consistent with a rapid equilibrium random mechanism.