The Interaction of Phosphoglucomutase with Nucleotide Inhibitors

Abstract

Phosphoglucomutases from rabbit muscle and Escherichia coli are inhibited by several nucleotides, the more potent of which are GDP, GTP, dTDP, Coenzyme A, and several CoA derivatives. Phosphoglucomutase from E. coli is somewhat more sensitive to the inhibitors than is the rabbit muscle enzyme. All of the inhibitors are noncompetitive with glucose 1,6-diphosphate and almost uncompetitive with glucose 1-phosphate as the varied substrates. Measurements of the relaxation rate of the solvent water protons in the presence of manganese complex of phosphoglucomutase from rabbit muscle and various combinations of substrates and inhibitors confirm observations in the literature that the relaxation enhancement due to the manganese-enzyme complex is greatly decreased when saturating amounts of glucose 1-phosphate and glucose 6-phosphate are added. When either ATP or acetyl-CoA is also present with the substrates, the decrease in relaxation enhancement is not as marked as in the presence of substrates alone. It is concluded from these studies and from titrations of the enzyme-manganese-substrate complexes with acetyl-CoA or GTP measuring the water proton relaxation rate that the inhibitors probably bind at a site on the enzyme surface which is distinct from the substrate binding site(s).