1exv
From Proteopedia
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HUMAN LIVER GLYCOGEN PHOSPHORYLASE A COMPLEXED WITH GLCNAC AND CP-403,700
Contents |
Overview
Background: Glycogen phosphorylases catalyze the breakdown of glycogen to, glucose-1-phosphate for glycolysis. Maintaining control of blood glucose, levels is critical in minimizing the debilitating effects of diabetes, making liver glycogen phosphorylase a potential therapeutic, target.Results: The binding site in human liver glycogen phosphorylase, (HLGP) for a class of promising antidiabetic agents was identified, crystallographically. The site is novel and functions allosterically by, stabilizing the inactive conformation of HLGP. The initial view of the, complex revealed key structural information and inspired the design of a, new class of inhibitors which bind with nanomolar affinity and whose, crystal structure is also described. Conclusions: We have identified the, binding site of a new class of allosteric HLGP inhibitors. The crystal, structure revealed the details of inhibitor binding, led to the design of, a new class of compounds, and should accelerate efforts to develop, therapeutically relevant molecules for the treatment of diabetes.
Disease
Known disease associated with this structure: Glycogen storage disease VI OMIM:[232700]
About this Structure
1EXV is a Single protein structure of sequence from Homo sapiens with NBG, PLP, 700 and MPD as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.
Reference
Human liver glycogen phosphorylase inhibitors bind at a new allosteric site., Rath VL, Ammirati M, Danley DE, Ekstrom JL, Gibbs EM, Hynes TR, Mathiowetz AM, McPherson RK, Olson TV, Treadway JL, Hoover DJ, Chem Biol. 2000 Sep;7(9):677-82. PMID:10980448
Page seeded by OCA on Mon Nov 12 16:47:33 2007
Categories: Homo sapiens | Phosphorylase | Single protein | Ammirati, M. | Danley, D.E. | Ekstrom, J.L. | Hoover, D.J. | Hynes, T.R. | Olson, T.V. | Rath, V.L. | 700 | MPD | NBG | PLP | Allosteric binding | Allosteric site
