3DD1

Crystal structure of glycogen phophorylase complexed with an anthranilimide based inhibitor GSK254

Summary for 3DD1

• Entry DOI: 10.2210/pdb3dd1/pdb
• Related: 3DDS 3DDW
• Descriptor: Glycogen phosphorylase, liver form, N-acetyl-beta-D-glucopyranosylamine, PYRIDOXAL-5'-PHOSPHATE, ... (8 entities in total)
• Functional Keywords: glycogen phosphorylase hlgp, diabetes, allosteric enzyme, carbohydrate metabolism, disease mutation, glycogen metabolism, glycogen storage disease, glycosyltransferase, nucleotide-binding, phosphoprotein, pyridoxal phosphate, transferase
• Biological source: Homo sapiens
• Total number of polymer chains: 2
• Total formula weight: 197988.36

Authors

Nolte, R.T. (deposition date: 2008-06-04, release date: 2009-04-21, Last modification date: 2023-08-30)

Primary citation

Thomson, S.A.,Banker, P.,Bickett, D.M.,Boucheron, J.A.,Carter, H.L.,Clancy, D.C.,Cooper, J.P.,Dickerson, S.H.,Garrido, D.M.,Nolte, R.T.,Peat, A.J.,Sheckler, L.R.,Sparks, S.M.,Tavares, F.X.,Wang, L.,Wang, T.Y.,Weiel, J.E.
Anthranilimide based glycogen phosphorylase inhibitors for the treatment of type 2 diabetes. Part 3: X-ray crystallographic characterization, core and urea optimization and in vivo efficacy.
Bioorg.Med.Chem.Lett., 19:1177-1182, 2009

PubMed Abstract: Key binding interactions of the anthranilimide based glycogen phosphorylase a (GPa) inhibitor 2 from X-ray crystallography studies are described. This series of compounds bind to the AMP site of GP. Using the binding information the core and the phenyl urea moieties were optimized. This work culminated in the identification of compounds with single nanomolar potency as well as in vivo efficacy in a diabetic model.

PubMed: 19138846
DOI: 10.1016/j.bmcl.2008.12.085

Experimental method

X-RAY DIFFRACTION (2.57 Å)