1C50

IDENTIFICATION AND STRUCTURAL CHARACTERIZATION OF A NOVEL ALLOSTERIC BINDING SITE OF GLYCOGEN PHOSPHORYLASE B

Summary for 1C50

• Entry DOI: 10.2210/pdb1c50/pdb
• Descriptor: PROTEIN (GLYCOGEN PHOSPHORYLASE), PYRIDOXAL-5'-PHOSPHATE, 5-CHLORO-1H-INDOLE-2-CARBOXYLIC ACID [1-(4-FLUOROBENZYL)-2-(4-HYDROXYPIPERIDIN-1YL)-2-OXOETHYL]AMIDE, ... (4 entities in total)
• Functional Keywords: glycogen metabolism, glycogen phosphorylase b, inhibition, central cavity, drug binding site, transferase
• Biological source: Oryctolagus cuniculus (rabbit)
• Total number of polymer chains: 1
• Total formula weight: 96524.60

Authors

Oikonomakos, N.G.,Skamnaki, V.T.,Tsitsanou, K.E.,Gavalas, N.G.,Johnson, L.N. (deposition date: 1999-12-15, release date: 1999-12-23, Last modification date: 2023-12-27)

Primary citation

Oikonomakos, N.G.,Skamnaki, V.T.,Tsitsanou, K.E.,Gavalas, N.G.,Johnson, L.N.
A new allosteric site in glycogen phosphorylase b as a target for drug interactions.
Structure Fold.Des., 8:575-584, 2000

PubMed Abstract: In muscle and liver, glycogen concentrations are regulated by the coordinated activities of glycogen phosphorylase (GP) and glycogen synthase. GP exists in two forms: the dephosphorylated low-activity form GPb and the phosphorylated high-activity form GPa. In both forms, allosteric effectors can promote equilibrium between a less active T state and a more active R state. GP is a possible target for drugs that aim to prevent unwanted glycogen breakdown and to stimulate glycogen synthesis in non-insulin-dependent diabetes. As a result of a data bank search, 5-chloro-1H-indole-2-carboxylic acid (1-(4-fluorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2-oxoethy l)amide, CP320626, was identified as a potent inhibitor of human liver GP. Structural studies have been carried out in order to establish the mechanism of this unusual inhibitor.

PubMed: 10873856
DOI: 10.1016/S0969-2126(00)00144-1

Experimental method

X-RAY DIFFRACTION (2.3 Å)