1L5Q

Human liver glycogen phosphorylase a complexed with caffeine, N-Acetyl-beta-D-glucopyranosylamine, and CP-403700

Summary for 1L5Q

• Entry DOI: 10.2210/pdb1l5q/pdb
• Related: 1L5R 1L5S 1L7X
• Descriptor: Glycogen phosphorylase, liver form, N-acetyl-beta-D-glucopyranosylamine, PYRIDOXAL-5'-PHOSPHATE, ... (6 entities in total)
• Functional Keywords: phosphorylase, purine site, transferase
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 197118.13

Authors

Ekstrom, J.L.,Pauly, T.A.,Carty, M.D.,Soeller, W.C.,Culp, J.,Danley, D.E.,Hoover, D.J.,Treadway, J.L.,Gibbs, E.M.,Fletterick, R.J.,Day, Y.S.N.,Myszka, D.G.,Rath, V.L. (deposition date: 2002-03-07, release date: 2002-12-04, Last modification date: 2020-07-29)

Primary citation

Ekstrom, J.L.,Pauly, T.A.,Carty, M.D.,Soeller, W.C.,Culp, J.,Danley, D.E.,Hoover, D.J.,Treadway, J.L.,Gibbs, E.M.,Fletterick, R.J.,Day, Y.S.,Myszka, D.G.,Rath, V.L.
Structure-activity analysis of the purine binding site of human liver glycogen phosphorylase.
Chem.Biol., 9:915-924, 2002

PubMed Abstract: 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.

PubMed: 12204691
DOI: 10.1016/S1074-5521(02)00186-2

Experimental method

X-RAY DIFFRACTION (2.25 Å)