1H5U

THE 1.76 A RESOLUTION CRYSTAL STRUCTURE OF GLYCOGEN PHOSPHORYLASE B COMPLEXED WITH GLUCOSE AND CP320626, A POTENTIAL ANTIDIABETIC DRUG

Summary for 1H5U

• Entry DOI: 10.2210/pdb1h5u/pdb
• Related: 1A8I 1ABB 1AXR 1B4D 1BX3 1C50 1C8K 1C8L 1E1Y 1FS4 1FTQ 1FTW 1FTY 1FU4 1FU7 1FU8 1GFZ 1GG8 1GGN 1GPA 1GPB 1GPY 1HLF 1NOI 1NOJ 1NOK 1PYG 2AMV 2GPA 2GPB 2GPN 2PRI 2PRJ 2SKC 2SKD 2SKE 3AMV 3GPB 4GPB 5GPB 6GPB 7GPB 8GPB 9GPB
• Descriptor: GLYCOGEN PHOSPHORYLASE, 5-CHLORO-1H-INDOLE-2-CARBOXYLIC ACID [1-(4-FLUOROBENZYL)-2-(4-HYDROXYPIPERIDIN-1YL)-2-OXOETHYL]AMIDE, alpha-D-glucopyranose, ... (5 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: 98162.40

Authors

Oikonomakos, N.G.,Zographos, S.E.,Skamnaki, V.T.,Archontis, G. (deposition date: 2001-05-25, release date: 2001-06-28, Last modification date: 2023-12-13)

Primary citation

Oikonomakos, N.G.,Zographos, S.E.,Skamnaki, V.T.,Archontis, G.
The 1.76 A Resolution Crystal Structure of Glycogen Phosphorylase B Complexed with Glucose, and Cp320626, a Potential Antidiabetic Drug
Bioorg.Med.Chem., 10:1313-, 2002

PubMed Abstract: CP320626, a potential antidiabetic drug, inhibits glycogen phosphorylase in synergism with glucose. To elucidate the structural basis of synergistic inhibition, we determined the structure of muscle glycogen phosphorylase b (MGPb) complexed with both glucose and CP320626 at 1.76 A resolution, and refined to a crystallographic R value of 0.211 (R(free)=0.235). CP320626 binds at a novel allosteric site, which is some 33 A from the catalytic site, where glucose binds. The high resolution structure allows unambiguous definition of the conformation of the 1-acetyl-4-hydroxy-piperidine ring supported by theoretical energy calculations. Both CP320626 and glucose promote the less active T-state, thereby explaining their synergistic inhibition. Structural comparison of MGPb--glucose--CP320626 complex with liver glycogen phosphorylase a (LGPa) complexed with a related compound (CP403700) show that the ligand binding site is conserved in LGPa.

PubMed: 11886794
DOI: 10.1016/S0968-0896(01)00394-7

Experimental method

X-RAY DIFFRACTION (1.76 Å)