2off
From Proteopedia
(New page: 200px<br /><applet load="2off" size="450" color="white" frame="true" align="right" spinBox="true" caption="2off, resolution 2.20Å" /> '''The crystal structur...) |
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| - | [[Image:2off.jpg|left|200px]]<br /><applet load="2off" size=" | + | [[Image:2off.jpg|left|200px]]<br /><applet load="2off" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2off, resolution 2.20Å" /> | caption="2off, resolution 2.20Å" /> | ||
'''The crystal structure of Glycogen Phosphorylase b in complex with a potent allosteric inhibitor'''<br /> | '''The crystal structure of Glycogen Phosphorylase b in complex with a potent allosteric inhibitor'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2OFF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with OFF as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 2OFF is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with <scene name='pdbligand=OFF:'>OFF</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OFF OCA]. |
==Reference== | ==Reference== | ||
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[[Category: type 2 diabetes]] | [[Category: type 2 diabetes]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:16:51 2008'' |
Revision as of 12:16, 23 January 2008
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The crystal structure of Glycogen Phosphorylase b in complex with a potent allosteric inhibitor
Overview
FR258900 has been discovered as a novel inhibitor of human liver glycogen, phosphorylase a and proved to suppress hepatic glycogen breakdown and, reduce plasma glucose concentrations in diabetic mice models. To elucidate, the mechanism of inhibition, we have determined the crystal structure of, the cocrystallized rabbit muscle glycogen phosphorylase b-FR258900 complex, and refined it to 2.2 A resolution. The structure demonstrates that the, inhibitor binds at the allosteric activator site, where the physiological, activator AMP binds. The contacts from FR258900 to glycogen phosphorylase, are dominated by nonpolar van der Waals interactions with Gln71, Gln72, Phe196, and Val45' (from the symmetry-related subunit), and also by ionic, interactions from the carboxylate groups to the three arginine residues, (Arg242, Arg309, and Arg310) that form the allosteric, phosphate-recognition subsite. The binding of FR258900 to the protein, promotes conformational changes that stabilize an inactive T-state, quaternary conformation of the enzyme. The ligand-binding mode is, different from those of the potent phenoxy-phthalate and acyl urea, inhibitors, previously described, illustrating the broad specificity of, the allosteric site.
About this Structure
2OFF is a Single protein structure of sequence from Oryctolagus cuniculus with as ligand. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.
Reference
FR258900, a potential anti-hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase., Tiraidis C, Alexacou KM, Zographos SE, Leonidas DD, Gimisis T, Oikonomakos NG, Protein Sci. 2007 Aug;16(8):1773-82. Epub 2007 Jun 28. PMID:17600143
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