Interaction of glycogen synthase from rabbit skeletal muscles with 1,5-gluconolactone

1.5-Gluconolactone was shown to inhibit in a competitive manner the activity of both I- and D-forms of rabbit skeletal muscle glycogen synthase. Unlike other known inhibitors (UDP and adenyl nucleotides) the affinity of the enzyme D-form for 1.5-gluconolactone is lower than that of the I-form. The joint inhibition of glycogen synthase by UDP and 1.5-gluconolactone is characterized by positive cooperativity. It was supposed that the binding of the nucleotide part of the substrate molecule is preceded by the UDPglucose glucosyl residue interaction with the enzyme and induces a closer resemblance to the transient state. The effect of the allosteric inhibitor, ADP, on the enzyme activity is conditioned by its effect on the conformational state of UDP-glucose glucosyl residue binding site. Phosphorylation of glycogen synthase results in conformational changes in the same active site region, although the pyrimidine base binding site also seems to be involved in this process.