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| - | [[Image:2ao0.gif|left|200px]]<br /><applet load="2ao0" size="450" color="white" frame="true" align="right" spinBox="true" | + | #REDIRECT [[3h4g]] This PDB entry is obsolete and replaced by 3h4g |
| - | caption="2ao0, resolution 1.85Å" />
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| - | '''Structure of Aldehyde Reductase Holoenzyme in Complex with the Potent Aldose Reductase Inhibitor Fidarestat: Implications for Inhibitor Binding and Selectivity'''<br />
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| - | ==Overview==
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| - | 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.
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| - | ==About this Structure==
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| - | 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2AO0 OCA].
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| - | ==Reference==
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| - | 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16107153 16107153]
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| - | [[Category: Alcohol dehydrogenase (NADP(+))]]
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| - | [[Category: Single protein]]
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| - | [[Category: Sus scrofa]]
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| - | [[Category: Carbone, V.]]
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| - | [[Category: Chung, R.P.]]
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| - | [[Category: Darmanin, C.]]
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| - | [[Category: El-Kabbani, O.]]
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| - | [[Category: Mitschler, A.]]
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| - | [[Category: Oka, M.]]
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| - | [[Category: Podjarny, A.]]
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| - | [[Category: Schulze-Briese, C.]]
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| - | [[Category: FID]]
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| - | [[Category: NAP]]
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| - | [[Category: SO4]]
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| - | [[Category: aldo-keto reductase]]
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| - | [[Category: ternary complex]]
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| - | [[Category: tim barrel]]
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| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 08:15:19 2007''
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