2gpb
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COMPARISON OF THE BINDING OF GLUCOSE AND GLUCOSE-1-PHOSPHATE DERIVATIVES TO T-STATE GLYCOGEN PHOSPHORYLASE B
OverviewOverview
The binding of T-state- and R-state-stabilizing ligands to the catalytic C, site of T-state glycogen phosphorylase b has been investigated by, crystallographic methods to study the interactions made and the, conformational changes that occur at the C site. The compounds studied, were alpha-D-glucose, 1, a T-state-stabilizing inhibitor of the enzyme, and the R-state-stabilizing phosphorylated ligands alpha-D-glucose, 1-phosphate (2), 2-deoxy-2-fluoro-alpha-D-glucose 1-phosphate (3), and, alpha-D-glucose 1-methylenephosphonate (4). The complexes have been, refined, giving crystallographic R factors of less than 19%, for data, between 8 and 2.3 A. Analysis of the refined structures shows that the, glucosyl portions of the phosphorylated ligands bind in the same, orientation as glucose and retain most of the interactions formed between, glucose and the enzyme. However, the phosphates of the phosphorylated, ligands adopt different conformations in each case; the stability of these, conformations have been studied by using computational methods to, rationalize the different binding modes. Binding of the phosphorylated, ligands is accompanied by movement of C-site residues, most notably a, shift of a loop out of the C site and toward the exterior of the protein., The C-site alterations do not include movement of Arg569, which has been, observed in both the refined complex with 1-deoxy-D-gluco-heptulose, 2-phosphate (5) [Johnson, L. N., et al (1990) J. Mol. Biol. 211, 645-661], and in the R-state enzyme [Barford, D. & Johnson, L. N. (1989) Nature 340, 609-616]. Refinement of the ligand complexes has also led to the, observation of additional electron density for residues 10-19 at the, N-terminus which had not previously been localized in the native, structure. The conformation of this stretch of residues is different from, that observed in glycogen phosphorylase a.
About this StructureAbout this Structure
2GPB is a Single protein structure of sequence from Oryctolagus cuniculus with GLC and PLP as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.
ReferenceReference
Comparison of the binding of glucose and glucose 1-phosphate derivatives to T-state glycogen phosphorylase b., Martin JL, Johnson LN, Withers SG, Biochemistry. 1990 Dec 4;29(48):10745-57. PMID:2125493
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