1wv0: Difference between revisions
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[[Image:1wv0.gif|left|200px]] | [[Image:1wv0.gif|left|200px]] | ||
'''Crystallographic studies on acyl ureas, a new class of inhibitors of glycogen phosphorylase. Broad specificity of the allosteric site''' | {{Structure | ||
|PDB= 1wv0 |SIZE=350|CAPTION= <scene name='initialview01'>1wv0</scene>, resolution 2.26Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> and <scene name='pdbligand=BN4:4-[4-({[(2,4-DICHLOROBENZOYL)AMINO]CARBONYL}AMINO)-2,3-DIMETHYLPHENOXY]BUTANOIC ACID'>BN4</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= | |||
}} | |||
'''Crystallographic studies on acyl ureas, a new class of inhibitors of glycogen phosphorylase. Broad specificity of the allosteric site''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1WV0 is a [ | 1WV0 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=1WV0 OCA]. | ||
==Reference== | ==Reference== | ||
Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs., Oikonomakos NG, Kosmopoulou MN, Chrysina ED, Leonidas DD, Kostas ID, Wendt KU, Klabunde T, Defossa E, Protein Sci. 2005 Jul;14(7):1760-71. PMID:[http:// | Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs., Oikonomakos NG, Kosmopoulou MN, Chrysina ED, Leonidas DD, Kostas ID, Wendt KU, Klabunde T, Defossa E, Protein Sci. 2005 Jul;14(7):1760-71. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15987904 15987904] | ||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Phosphorylase]] | [[Category: Phosphorylase]] | ||
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[[Category: type 2 diabetes]] | [[Category: type 2 diabetes]] | ||
''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 15:01:51 2008'' | ||
Revision as of 16:01, 20 March 2008
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| , resolution 2.26Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Phosphorylase, with EC number 2.4.1.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystallographic studies on acyl ureas, a new class of inhibitors of glycogen phosphorylase. Broad specificity of the allosteric site
OverviewOverview
Acyl ureas were discovered as a novel class of inhibitors for glycogen phosphorylase, a molecular target to control hyperglycemia in type 2 diabetics. This series is exemplified by 6-{2,6-Dichloro- 4-[3-(2-chloro-benzoyl)-ureido]-phenoxy}-hexanoic acid, which inhibits human liver glycogen phosphorylase a with an IC(50) of 2.0 microM. Here we analyze four crystal structures of acyl urea derivatives in complex with rabbit muscle glycogen phosphorylase b to elucidate the mechanism of inhibition of these inhibitors. The structures were determined and refined to 2.26 Angstroms resolution and demonstrate that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Acyl ureas induce conformational changes in the vicinity of the allosteric site. Our findings suggest that acyl ureas inhibit glycogen phosphorylase by direct inhibition of AMP binding and by indirect inhibition of substrate binding through stabilization of the T' state.
About this StructureAbout this Structure
1WV0 is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
ReferenceReference
Crystallographic studies on acyl ureas, a new class of glycogen phosphorylase inhibitors, as potential antidiabetic drugs., Oikonomakos NG, Kosmopoulou MN, Chrysina ED, Leonidas DD, Kostas ID, Wendt KU, Klabunde T, Defossa E, Protein Sci. 2005 Jul;14(7):1760-71. PMID:15987904
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