1h5u
From Proteopedia
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THE 1.76 A RESOLUTION CRYSTAL STRUCTURE OF GLYCOGEN PHOSPHORYLASE B COMPLEXED WITH GLUCOSE AND CP320626, A POTENTIAL ANTIDIABETIC DRUG
Overview
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.
About this Structure
1H5U is a Single protein structure of sequence from Oryctolagus cuniculus with GLC, CHI and PLP as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Structure known Active Sites: CHI, GLC and PLP. Full crystallographic information is available from OCA.
Reference
The 1.76 A resolution crystal structure of glycogen phosphorylase B complexed with glucose, and CP320626, a potential antidiabetic drug., Oikonomakos NG, Zographos SE, Skamnaki VT, Archontis G, Bioorg Med Chem. 2002 May;10(5):1313-9. PMID:11886794
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