1wv1: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 1wv1 |SIZE=350|CAPTION= <scene name='initialview01'>1wv1</scene>, resolution 2.26Å | |PDB= 1wv1 |SIZE=350|CAPTION= <scene name='initialview01'>1wv1</scene>, resolution 2.26Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=PLP:PYRIDOXAL-5 | |LIGAND= <scene name='pdbligand=PLP:PYRIDOXAL-5'-PHOSPHATE'>PLP</scene> and <scene name='pdbligand=BN5:5-[3-({[(2,4-DICHLOROBENZOYL)AMINO]CARBONYL}AMINO)-2-METHYLPHENOXY]PENTANOIC ACID'>BN5</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= [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= | |GENE= | ||
| Line 35: | Line 35: | ||
[[Category: type 2 diabetes]] | [[Category: type 2 diabetes]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 14:09:18 2008'' | ||
Revision as of 15:09, 23 March 2008
| |||||||
| , 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 glycogenphosphorylase. 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
1WV1 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
Page seeded by OCA on Sun Mar 23 14:09:18 2008