1k06

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spinqualitylabelsall models 1k06, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystallographic Binding Study of 100 mM N-benzoyl-N'-beta-D-glucopyranosyl urea to glycogen phosphorylase b

Overview

Two substituted ureas of beta-D-glucose, N-acetyl-N'-beta-D-glucopyranosyl, urea (Acurea) and N-benzoyl-N'-beta-D-glucopyranosyl urea (Bzurea), have, been identified as inhibitors of glycogen phosphorylase, a potential, target for therapeutic intervention in type 2 diabetes. To elucidate the, structural basis of inhibition, we determined the structure of muscle, glycogen phosphorylase b (GPb) complexed with the two compounds at 2.0 A, and 1.8 A resolution, respectively. The structure of the GPb-Acurea, complex reveals that the inhibitor can be accommodated in the catalytic, site of T-state GPb with very little change in the tertiary structure. The, glucopyranose moiety makes the standard hydrogen bonds and van der Waals, contacts as observed in the GPb-glucose complex, while the acetyl urea, moiety is in a favourable electrostatic environment and makes additional, polar contacts with the protein. The structure of the GPb-Bzurea complex, shows that Bzurea binds tightly at the catalytic site and induces, substantial conformational changes in the vicinity of the catalytic site., In particular, the loop of the polypeptide chain containing residues, 282-287 shifts 1.3-3.7 A (Calpha atoms) to accommodate Bzurea. Bzurea can, also occupy the new allosteric site, some 33 A from the catalytic site, which is currently the target for the design of antidiabetic drugs.

About this Structure

1K06 is a Single protein structure of sequence from Oryctolagus cuniculus with BZD and PLP as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.

Reference

Binding of N-acetyl-N '-beta-D-glucopyranosyl urea and N-benzoyl-N '-beta-D-glucopyranosyl urea to glycogen phosphorylase b: kinetic and crystallographic studies., Oikonomakos NG, Kosmopoulou M, Zographos SE, Leonidas DD, Chrysina ED, Somsak L, Nagy V, Praly JP, Docsa T, Toth B, Gergely P, Eur J Biochem. 2002 Mar;269(6):1684-96. PMID:11895439

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