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| | <StructureSection load='2f2k' size='340' side='right'caption='[[2f2k]], [[Resolution|resolution]] 1.94Å' scene=''> | | <StructureSection load='2f2k' size='340' side='right'caption='[[2f2k]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2f2k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F2K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2f2k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F2K FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=TGG:GAMMA-GLUTAMYL-S-(1,2-DICARBOXYETHYL)CYSTEINYLGLYCINE'>TGG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ads|1ads]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=TGG:GAMMA-GLUTAMYL-S-(1,2-DICARBOXYETHYL)CYSTEINYLGLYCINE'>TGG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AKR1B1, ALDR1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.21 1.1.1.21] </span></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=2f2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f2k OCA], [https://pdbe.org/2f2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f2k RCSB], [https://www.ebi.ac.uk/pdbsum/2f2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f2k ProSAT]</span></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=2f2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f2k OCA], [https://pdbe.org/2f2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f2k RCSB], [https://www.ebi.ac.uk/pdbsum/2f2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f2k ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ALDR_HUMAN ALDR_HUMAN]] Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
| + | [https://www.uniprot.org/uniprot/ALDR_HUMAN ALDR_HUMAN] Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Aldehyde reductase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bhatnagar, A]] | + | [[Category: Bhatnagar A]] |
| - | [[Category: Petrash, J M]] | + | [[Category: Petrash JM]] |
| - | [[Category: Ramana, K V]] | + | [[Category: Ramana KV]] |
| - | [[Category: Singh, R]] | + | [[Category: Singh R]] |
| - | [[Category: Srivastava, S K]] | + | [[Category: Srivastava SK]] |
| - | [[Category: Watowich, S J]] | + | [[Category: Watowich SJ]] |
| - | [[Category: White, M A]] | + | [[Category: White MA]] |
| - | [[Category: Dicarboxyethyl glutathione]]
| + | |
| - | [[Category: Glutathione]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Tertiary complex]]
| + | |
| Structural highlights
Function
ALDR_HUMAN Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Aldose reductase (AR) is a monomeric NADPH-dependent oxidoreductase that catalyzes the reduction of aldehydes, ketones, and aldo-sugars. AR has been linked to the development of hyperglycemic injury and is a clinical target for the treatment of secondary diabetic complications. In addition to reducing glucose, AR is key regulator of cell signaling through it's reduction of aldehydes derived from lipoproteins and membrane phospholipids. AR catalyzes the reduction of glutathione conjugates of unsaturated aldehydes with higher catalytic efficiency than free aldehydes. The X-ray structure of human AR holoenzyme in complex with the glutathione analogue S-(1,2-dicarboxyethyl) glutathione (DCEG) was determined at a resolution of 1.94 A. The distal carboxylate group of DCEG's dicarboxyethyl moiety interacted with the conserved AR anion binding site residues Tyr48, His110, and Trp111. The bound DCEG's glutathione backbone adopted the low-energy Y-shape form. The C-terminal carboxylate of DCEG glutathione's glycine formed hydrogen bonds to Leu301 and Ser302, while the remaining interactions between DCEG and AR were hydrophobic, permitting significant flexibility of the AR and glutathione (GS) analogue interaction. The observed conformation and interactions of DCEG with AR were consistent with our previously published molecular dynamics model of glutathionyl-propanal binding to AR. The current structure identifies major interactions of glutathione conjugates with the AR active-site residues.
Structure of a glutathione conjugate bound to the active site of aldose reductase.,Singh R, White MA, Ramana KV, Petrash JM, Watowich SJ, Bhatnagar A, Srivastava SK Proteins. 2006 Jul 1;64(1):101-10. PMID:16639747[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Singh R, White MA, Ramana KV, Petrash JM, Watowich SJ, Bhatnagar A, Srivastava SK. Structure of a glutathione conjugate bound to the active site of aldose reductase. Proteins. 2006 Jul 1;64(1):101-10. PMID:16639747 doi:10.1002/prot.20988
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