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1h5u

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{{STRUCTURE_1h5u| PDB=1h5u | SCENE= }}
{{STRUCTURE_1h5u| PDB=1h5u | SCENE= }}
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'''THE 1.76 A RESOLUTION CRYSTAL STRUCTURE OF GLYCOGEN PHOSPHORYLASE B COMPLEXED WITH GLUCOSE AND CP320626, A POTENTIAL ANTIDIABETIC DRUG'''
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===THE 1.76 A RESOLUTION CRYSTAL STRUCTURE OF GLYCOGEN PHOSPHORYLASE B COMPLEXED WITH GLUCOSE AND CP320626, A POTENTIAL ANTIDIABETIC DRUG===
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==Overview==
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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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{{ABSTRACT_PUBMED_11886794}}
==About this Structure==
==About this Structure==
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[[Category: Inhibition]]
[[Category: Inhibition]]
[[Category: Transferase]]
[[Category: Transferase]]
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Revision as of 03:40, 1 July 2008

Image:1h5u.png

Template:STRUCTURE 1h5u

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

Template:ABSTRACT PUBMED 11886794

About this Structure

1H5U is a Single protein structure of sequence from Oryctolagus cuniculus. 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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