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B6db references: 21883609

type Journal Article
authors Oikonomakos, N. G.; Zographos, S. E.; Skamnaki, V. T.; Archontis, G.
title The 1.76 A Resolution Crystal Structure of Glycogen Phosphorylase b Complexed with Glucose, and CP320626, a Potential Antidiabetic Drug
journal Bioorg Med Chem
ui 21883609
year (2002)
volume 10
number 5
pages 1313-9.
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.
last changed 2002/11/12 16:17

B6db references