1h5u
From Proteopedia
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|PDB= 1h5u |SIZE=350|CAPTION= <scene name='initialview01'>1h5u</scene>, resolution 1.76Å | |PDB= 1h5u |SIZE=350|CAPTION= <scene name='initialview01'>1h5u</scene>, resolution 1.76Å | ||
|SITE= <scene name='pdbsite=CHI:Chi/Cp320626+Binding+Site'>CHI</scene>, <scene name='pdbsite=GLC:Glc+Binding+Site+For+Chain+A'>GLC</scene> and <scene name='pdbsite=PLP:Plp+Binding+Site+For+Chain+A'>PLP</scene> | |SITE= <scene name='pdbsite=CHI:Chi/Cp320626+Binding+Site'>CHI</scene>, <scene name='pdbsite=GLC:Glc+Binding+Site+For+Chain+A'>GLC</scene> and <scene name='pdbsite=PLP:Plp+Binding+Site+For+Chain+A'>PLP</scene> | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=CHI:5-CHLORO-1H-INDOLE-2-CARBOXYLIC+ACID+[1-(4-FLUOROBENZYL)-2-(4-HYDROXYPIPERIDIN-1YL)-2-OXOETHYL]AMIDE'>CHI</scene>, <scene name='pdbligand=GLC:GLUCOSE'>GLC</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphorylase Phosphorylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.1 2.4.1.1] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h5u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h5u OCA], [http://www.ebi.ac.uk/pdbsum/1h5u PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h5u RCSB]</span> | ||
}} | }} | ||
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[[Category: Skamnaki, V T.]] | [[Category: Skamnaki, V T.]] | ||
[[Category: Zographos, S E.]] | [[Category: Zographos, S E.]] | ||
| - | [[Category: CHI]] | ||
| - | [[Category: GLC]] | ||
| - | [[Category: PLP]] | ||
[[Category: central cavity]] | [[Category: central cavity]] | ||
[[Category: drug binding site]] | [[Category: drug binding site]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:58:21 2008'' |
Revision as of 17:58, 30 March 2008
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| , resolution 1.76Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | , and | ||||||
| Ligands: | , , | ||||||
| Activity: | Phosphorylase, with EC number 2.4.1.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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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