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Updated: Oct 2, 2026

Spectrophotometric Methods for the Study of Eukaryotic Glycogen Metabolism
Published on: August 19, 2021
The 1.76 A resolution crystal structure of glycogen phosphorylase B complexed with glucose, and CP320626, a potential
Nikos G Oikonomakos1, Spyros E Zographos, Vicky T Skamnaki
1Institute of Biological Research and Biotechnology, The National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, Athens 11635, Greece. ngo@eie.gr
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.
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