1c50: Difference between revisions
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[[Image:1c50.gif|left|200px]] | [[Image:1c50.gif|left|200px]] | ||
'''IDENTIFICATION AND STRUCTURAL CHARACTERIZATION OF A NOVEL ALLOSTERIC BINDING SITE OF GLYCOGEN PHOSPHORYLASE B''' | {{Structure | ||
|PDB= 1c50 |SIZE=350|CAPTION= <scene name='initialview01'>1c50</scene>, resolution 2.3Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> and <scene name='pdbligand=CHI:5-CHLORO-1H-INDOLE-2-CARBOXYLIC ACID [1-(4-FLUOROBENZYL)-2-(4-HYDROXYPIPERIDIN-1YL)-2-OXOETHYL]AMIDE'>CHI</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] | |||
|GENE= | |||
}} | |||
'''IDENTIFICATION AND STRUCTURAL CHARACTERIZATION OF A NOVEL ALLOSTERIC BINDING SITE OF GLYCOGEN PHOSPHORYLASE B''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1C50 is a [ | 1C50 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C50 OCA]. | ||
==Reference== | ==Reference== | ||
A new allosteric site in glycogen phosphorylase b as a target for drug interactions., Oikonomakos NG, Skamnaki VT, Tsitsanou KE, Gavalas NG, Johnson LN, Structure. 2000 Jun 15;8(6):575-84. PMID:[http:// | A new allosteric site in glycogen phosphorylase b as a target for drug interactions., Oikonomakos NG, Skamnaki VT, Tsitsanou KE, Gavalas NG, Johnson LN, Structure. 2000 Jun 15;8(6):575-84. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/10873856 10873856] | ||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Phosphorylase]] | [[Category: Phosphorylase]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:19:53 2008'' | ||
Revision as of 11:19, 20 March 2008
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| , resolution 2.3Å | |||||||
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| Ligands: | and | ||||||
| Activity: | Phosphorylase, with EC number 2.4.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
IDENTIFICATION AND STRUCTURAL CHARACTERIZATION OF A NOVEL ALLOSTERIC BINDING SITE OF GLYCOGEN PHOSPHORYLASE B
OverviewOverview
BACKGROUND: In muscle and liver, glycogen concentrations are regulated by the coordinated activities of glycogen phosphorylase (GP) and glycogen synthase. GP exists in two forms: the dephosphorylated low-activity form GPb and the phosphorylated high-activity form GPa. In both forms, allosteric effectors can promote equilibrium between a less active T state and a more active R state. GP is a possible target for drugs that aim to prevent unwanted glycogen breakdown and to stimulate glycogen synthesis in non-insulin-dependent diabetes. As a result of a data bank search, 5-chloro-1H-indole-2-carboxylic acid (1-(4-fluorobenzyl)-2-(4-hydroxypiperidin-1-yl)-2-oxoethy l)amide, CP320626, was identified as a potent inhibitor of human liver GP. Structural studies have been carried out in order to establish the mechanism of this unusual inhibitor. RESULTS: The structure of the cocrystallised GPb-CP320626 complex has been determined to 2.3 A resolution. CP320626 binds at a site located at the subunit interface in the region of the central cavity of the dimeric structure. The site has not previously been observed to bind ligands and is some 15 A from the AMP allosteric site and 33 A from the catalytic site. The contacts between GPb and CP320626 comprise six hydrogen bonds and extensive van der Waals interactions that create a tight binding site in the T-state conformation of GPb. In the R-state conformation of GPa these interactions are significantly diminished. CONCLUSIONS: CP320626 inhibits GPb by binding at a new allosteric site. Although over 30 A from the catalytic site, the inhibitor exerts its effects by stabilising the T state at the expense of the R state and thereby shifting the allosteric equilibrium between the two states. The new allosteric binding site offers a further recognition site in the search for improved GP inhibitors.
About this StructureAbout this Structure
1C50 is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
ReferenceReference
A new allosteric site in glycogen phosphorylase b as a target for drug interactions., Oikonomakos NG, Skamnaki VT, Tsitsanou KE, Gavalas NG, Johnson LN, Structure. 2000 Jun 15;8(6):575-84. PMID:10873856
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