1gpy
CRYSTALLOGRAPHIC BINDING STUDIES ON THE ALLOSTERIC INHIBITOR GLUCOSE-6-PHOSPHATE TO T STATE GLYCOGEN PHOSPHORYLASE B
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OverviewOverview
Glucose-6-phosphate is an important allosteric inhibitor of glycogen, phosphorylase b that restrains the enzyme in the inactive state in resting, muscle. A crystallographic binding study by diffusion of, glucose-6-phosphate into performed crystals of T state phosphorylase b has, been carried out at 2.3 A resolution and the structure refined by, restrained crystallographic least-squares and simulated annealing to give, a crystallographic R-value of 0.203. The inhibitor binds at the AMP, allosteric effector site at the subunit-subunit interface of the dimer., The phosphate groups of the glucose-6-phosphate and AMP occupy partially, overlapping sites and make similar contacts to two arginine residues, (Arg309 and Arg310) but in glucose-6-phosphate there is a contact to a, third arginine (Arg242). The glucopyranose of glucose-6-phosphate and the, adenine ribose of AMP occupy different positions. Including the contacts, to the three arginine residues by the phosphate group, the, glucose-6-phosphate makes a total of 11 hydrogen-bonds to the enzyme and, all but one of these are to charged groups. The O-2 hydroxyl, hydrogen-bonds to the main-chain carbonyl oxygen of Val40' from the other, subunit and this interaction appears important for the allosteric, response. There are substantial conformational changes both in the, vicinity of the glucose-6-phosphate (involving for example Phe196 and, Arg309) and at the subunit interface (involving residues 42' to 51' and, 192 to 196). These shifts tighten the binding of the inhibitor and the, interface. Comparison of the glucose-6-phosphate complex with the T state, native phosphorylase b and the R state phosphorylase a structures shows, that there is a graded response from T state glucose-6-phosphate complex, through T state phosphorylase b to R state phosphorylase a that suggests, that glucose-6-phosphate promotes a tight structure that is more "tensed", than native T state phosphorylase b. The results show how the same, allosteric effector site can exhibit a tight binding site for the, activator AMP in the R state structure and a tight binding site for, glucose-6-phosphate in the modified T state structure.
About this StructureAbout this Structure
1GPY is a Single protein structure of sequence from Oryctolagus cuniculus with G6P and PLP as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Crystallographic binding studies on the allosteric inhibitor glucose-6-phosphate to T state glycogen phosphorylase b., Johnson LN, Snape P, Martin JL, Acharya KR, Barford D, Oikonomakos NG, J Mol Biol. 1993 Jul 5;232(1):253-67. PMID:8331662
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