1l5r: Difference between revisions

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.

[[Category: Carty, M D.]]

[[Category: Danley, D E.]]

[[Category: Day, Y S.N.]]

[[Category: Ekstrom, J L.]]

[[Category: Fletterick, R J.]]

[[Category: Gibbs, E M.]]

[[Category: Hoover, D J.]]

[[Category: Myszka, D G.]]

[[Category: Pauly, T A.]]

[[Category: Rath, V L.]]

[[Category: Soeller, W C.]]

[[Category: Treadway, J L.]]

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