2ao0
From Proteopedia
(New page: 200px<br /><applet load="2ao0" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ao0, resolution 1.85Å" /> '''Structure of Aldehyd...) |
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| - | [[Image:2ao0.gif|left|200px]]<br /><applet load="2ao0" size=" | + | [[Image:2ao0.gif|left|200px]]<br /><applet load="2ao0" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2ao0, resolution 1.85Å" /> | caption="2ao0, resolution 1.85Å" /> | ||
'''Structure of Aldehyde Reductase Holoenzyme in Complex with the Potent Aldose Reductase Inhibitor Fidarestat: Implications for Inhibitor Binding and Selectivity'''<br /> | '''Structure of Aldehyde Reductase Holoenzyme in Complex with the Potent Aldose Reductase Inhibitor Fidarestat: Implications for Inhibitor Binding and Selectivity'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Structure determination of porcine aldehyde reductase holoenzyme in | + | Structure determination of porcine aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat was carried out to explain the difference in the potency of the inhibitor for aldose and aldehyde reductases. The hydrogen bonds between the active-site residues Tyr50, His113, and Trp114 and fidarestat are conserved in the two enzymes. In aldose reductase, Leu300 forms a hydrogen bond through its main-chain nitrogen atom with the exocyclic amide group of the inhibitor, which when replaced with a Pro in aldehyde reductase, cannot form a hydrogen bond, thus causing a loss in binding energy. Furthermore, in aldehyde reductase, the side chain of Trp220 occupies a disordered split conformation that is not observed in aldose reductase. Molecular modeling and inhibitory activity measurements suggest that the difference in the interaction between the side chain of Trp220 and fidarestat may contribute to the difference in the binding of the inhibitor to the enzymes. |
==About this Structure== | ==About this Structure== | ||
| - | 2AO0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with SO4, NAP and FID as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase_(NADP(+)) Alcohol dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.2 1.1.1.2] Full crystallographic information is available from [http:// | + | 2AO0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=SO4:'>SO4</scene>, <scene name='pdbligand=NAP:'>NAP</scene> and <scene name='pdbligand=FID:'>FID</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Alcohol_dehydrogenase_(NADP(+)) Alcohol dehydrogenase (NADP(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.2 1.1.1.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AO0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
[[Category: Carbone, V.]] | [[Category: Carbone, V.]] | ||
| - | [[Category: Chung, R | + | [[Category: Chung, R P.]] |
[[Category: Darmanin, C.]] | [[Category: Darmanin, C.]] | ||
[[Category: El-Kabbani, O.]] | [[Category: El-Kabbani, O.]] | ||
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[[Category: tim barrel]] | [[Category: tim barrel]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:29:14 2008'' |
Revision as of 14:29, 21 February 2008
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Structure of Aldehyde Reductase Holoenzyme in Complex with the Potent Aldose Reductase Inhibitor Fidarestat: Implications for Inhibitor Binding and Selectivity
Overview
Structure determination of porcine aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat was carried out to explain the difference in the potency of the inhibitor for aldose and aldehyde reductases. The hydrogen bonds between the active-site residues Tyr50, His113, and Trp114 and fidarestat are conserved in the two enzymes. In aldose reductase, Leu300 forms a hydrogen bond through its main-chain nitrogen atom with the exocyclic amide group of the inhibitor, which when replaced with a Pro in aldehyde reductase, cannot form a hydrogen bond, thus causing a loss in binding energy. Furthermore, in aldehyde reductase, the side chain of Trp220 occupies a disordered split conformation that is not observed in aldose reductase. Molecular modeling and inhibitory activity measurements suggest that the difference in the interaction between the side chain of Trp220 and fidarestat may contribute to the difference in the binding of the inhibitor to the enzymes.
About this Structure
2AO0 is a Single protein structure of sequence from Sus scrofa with , and as ligands. Active as Alcohol dehydrogenase (NADP(+)), with EC number 1.1.1.2 Full crystallographic information is available from OCA.
Reference
Structure of aldehyde reductase holoenzyme in complex with the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity., El-Kabbani O, Carbone V, Darmanin C, Oka M, Mitschler A, Podjarny A, Schulze-Briese C, Chung RP, J Med Chem. 2005 Aug 25;48(17):5536-42. PMID:16107153
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