2ieg
From Proteopedia
(New page: 200px<br /><applet load="2ieg" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ieg, resolution 1.90Å" /> '''Crystal structure of...) |
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| - | [[Image:2ieg.gif|left|200px]]<br /><applet load="2ieg" size=" | + | [[Image:2ieg.gif|left|200px]]<br /><applet load="2ieg" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2ieg, resolution 1.90Å" /> | caption="2ieg, resolution 1.90Å" /> | ||
'''Crystal structure of rabbit muscle glycogen phosphorylase in complex with 3,4-dihydro-2-quinolone'''<br /> | '''Crystal structure of rabbit muscle glycogen phosphorylase in complex with 3,4-dihydro-2-quinolone'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A series of substituted 3,4-dihydro-2-quinolone glycogen phosphorylase | + | A series of substituted 3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors, which have potential as antidiabetic agents, is described. Initial members of the series showed good enzyme inhibitory potency but poor physical properties. Optimisation of the 1-substituent led to 2,3-dihydroxypropyl compounds which showed good in vitro potency and improved physical properties, together with good DMPK profiles and acute in vivo efficacy in a rat model. X-ray crystallographic data are presented, showing an unexpected variety of binding orientations at the dimer interface site. |
==About this Structure== | ==About this Structure== | ||
| - | 2IEG 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 PLR and FRY as [http://en.wikipedia.org/wiki/ligands ligands]. 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:// | + | 2IEG 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=PLR:'>PLR</scene> and <scene name='pdbligand=FRY:'>FRY</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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=2IEG OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Phosphorylase]] | [[Category: Phosphorylase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Birch, A | + | [[Category: Birch, A M.]] |
[[Category: Breed, J.]] | [[Category: Breed, J.]] | ||
| - | [[Category: Kenny, P | + | [[Category: Kenny, P W.]] |
[[Category: Minshull, C.]] | [[Category: Minshull, C.]] | ||
| - | [[Category: Oikonomakos, N | + | [[Category: Oikonomakos, N G.]] |
[[Category: Otterbein, L.]] | [[Category: Otterbein, L.]] | ||
[[Category: Pannifer, A.]] | [[Category: Pannifer, A.]] | ||
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[[Category: Rowsell, S.]] | [[Category: Rowsell, S.]] | ||
[[Category: Schofield, P.]] | [[Category: Schofield, P.]] | ||
| - | [[Category: Whalley, D | + | [[Category: Whalley, D P.]] |
| - | [[Category: Whittamore, P | + | [[Category: Whittamore, P R.O.]] |
[[Category: FRY]] | [[Category: FRY]] | ||
[[Category: PLR]] | [[Category: PLR]] | ||
| Line 32: | Line 32: | ||
[[Category: glypho]] | [[Category: glypho]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:51:50 2008'' |
Revision as of 15:51, 21 February 2008
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Crystal structure of rabbit muscle glycogen phosphorylase in complex with 3,4-dihydro-2-quinolone
Overview
A series of substituted 3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors, which have potential as antidiabetic agents, is described. Initial members of the series showed good enzyme inhibitory potency but poor physical properties. Optimisation of the 1-substituent led to 2,3-dihydroxypropyl compounds which showed good in vitro potency and improved physical properties, together with good DMPK profiles and acute in vivo efficacy in a rat model. X-ray crystallographic data are presented, showing an unexpected variety of binding orientations at the dimer interface site.
About this Structure
2IEG is a Single protein structure of sequence from Oryctolagus cuniculus with and as ligands. Active as Phosphorylase, with EC number 2.4.1.1 Full crystallographic information is available from OCA.
Reference
Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors., Birch AM, Kenny PW, Oikonomakos NG, Otterbein L, Schofield P, Whittamore PR, Whalley DP, Bioorg Med Chem Lett. 2007 Jan 15;17(2):394-9. Epub 2006 Oct 19. PMID:17095214
Page seeded by OCA on Thu Feb 21 17:51:50 2008
Categories: Oryctolagus cuniculus | Phosphorylase | Single protein | Birch, A M. | Breed, J. | Kenny, P W. | Minshull, C. | Oikonomakos, N G. | Otterbein, L. | Pannifer, A. | Pauptit, R. | Rowsell, S. | Schofield, P. | Whalley, D P. | Whittamore, P R.O. | FRY | PLR | Diabetes | Glycogen phosphorylase | Glypho
