1l7x

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spinqualitylabelsall models 1l7x, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Human liver glycogen phosphorylase b complexed with caffeine, N-acetyl-beta-D-glucopyranosylamine, and CP-403,700

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Human liver glycogen phosphorylase (HLGP) catalyzes the breakdown of, glycogen to maintain serum glucose levels and is a therapeutic target for, diabetes. HLGP is regulated by multiple interacting allosteric sites, each, of which is a potential drug binding site. We used surface plasmon, resonance (SPR) to screen for compounds that bind to the purine allosteric, inhibitor site. We determined the affinities of a series of compounds and, solved the crystal structures of three representative ligands with K(D), values from 17-550 microM. The crystal structures reveal that the, affinities are partly determined by ligand-specific water-mediated, hydrogen bonds and side chain movements. These effects could not be, predicted; both crystallographic and SPR studies were required to, understand the important features of binding and together provide a basis, for the design of new allosteric inhibitors targeting this site.

Disease

Known disease associated with this structure: Glycogen storage disease VI OMIM:[232700]

About this Structure

1L7X is a Single protein structure of sequence from Homo sapiens with NBG, PLP, 700, CFF and MRD as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.

Reference

Structure-activity analysis of the purine binding site of human liver glycogen phosphorylase., Ekstrom JL, Pauly TA, Carty MD, Soeller WC, Culp J, Danley DE, Hoover DJ, Treadway JL, Gibbs EM, Fletterick RJ, Day YS, Myszka DG, Rath VL, Chem Biol. 2002 Aug;9(8):915-24. PMID:12204691

Page seeded by OCA on Mon Nov 12 17:57:31 2007