3h4g
From Proteopedia
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| - | [[Image:3h4g.png|left|200px]] | ||
| - | + | ==Structure of aldehyde reductase holoenzyme in complex with potent aldose reductase inhibitor Fidarestat: Implications for inhibitor binding and selectivity== | |
| + | <StructureSection load='3h4g' size='340' side='right'caption='[[3h4g]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3h4g]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2ao0 2ao0]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3H4G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H4G FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FID:(2S,4S)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4-IMIDAZOLIDINE]-2,5-DIONE'>FID</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3h4g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h4g OCA], [https://pdbe.org/3h4g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h4g RCSB], [https://www.ebi.ac.uk/pdbsum/3h4g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h4g ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/AK1A1_PIG AK1A1_PIG] Catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. Catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyde to glycerol. Has broad substrate specificity. Plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs (By similarity). | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h4/3h4g_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3h4g ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | 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. | ||
| - | + | 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<ref>PMID:16107153</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3h4g" style="background-color:#fffaf0;"></div> | |
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==See Also== | ==See Also== | ||
| - | *[[Alcohol dehydrogenase|Alcohol dehydrogenase]] | + | *[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]] |
| - | *[[Aldose | + | *[[Aldose reductase 3D structures|Aldose reductase 3D structures]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Sus scrofa]] | [[Category: Sus scrofa]] | ||
| - | [[Category: Carbone | + | [[Category: Carbone V]] |
| - | [[Category: El-Kabbani | + | [[Category: El-Kabbani O]] |
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Current revision
Structure of aldehyde reductase holoenzyme in complex with potent aldose reductase inhibitor Fidarestat: Implications for inhibitor binding and selectivity
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