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==Crystal Structure of Human Aldose Reductase Complexed with Sulindac Sulfone== | ==Crystal Structure of Human Aldose Reductase Complexed with Sulindac Sulfone== | ||
<StructureSection load='3rx2' size='340' side='right' caption='[[3rx2]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='3rx2' size='340' side='right'caption='[[3rx2]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3rx2]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3rx2]] 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=3RX2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RX2 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SLO:2-[(3Z)-6-FLUORANYL-2-METHYL-3-[(4-METHYLSULFONYLPHENYL)METHYLIDENE]INDEN-1-YL]ETHANOIC+ACID'>SLO</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SLO:2-[(3Z)-6-FLUORANYL-2-METHYL-3-[(4-METHYLSULFONYLPHENYL)METHYLIDENE]INDEN-1-YL]ETHANOIC+ACID'>SLO</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rx3|3rx3]], [[3rx4|3rx4]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3rx3|3rx3]], [[3rx4|3rx4]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AKR1B1, ALDR1 ([ | <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'>[ | <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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rx2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rx2 OCA], [https://pdbe.org/3rx2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rx2 RCSB], [https://www.ebi.ac.uk/pdbsum/3rx2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rx2 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. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Aldose | *[[Aldose reductase 3D structures|Aldose reductase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 30: | Line 30: | ||
[[Category: Aldehyde reductase]] | [[Category: Aldehyde reductase]] | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Chen, J]] | [[Category: Chen, J]] | ||
[[Category: Hu, X]] | [[Category: Hu, X]] | ||
Revision as of 13:28, 22 June 2022
Crystal Structure of Human Aldose Reductase Complexed with Sulindac SulfoneCrystal Structure of Human Aldose Reductase Complexed with Sulindac Sulfone
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. Publication Abstract from PubMedSulindac (SLD) exhibits both the highest inhibitory activity towards human aldose reductase (AR) among popular non-steroidal anti-inflammatory drugs and clear beneficial clinical effects on Type 2 diabetes. However, the molecular basis for these properties is unclear. Here, we report that SLD and its pharmacologically active/inactive metabolites, SLD sulfide and SLD sulfone, are equally effective as un-competitive inhibitors of AR in vitro. Crystallographic analysis reveals that pi-pi stacking favored by the distinct scaffold of SLDs is pivotal to their high AR inhibitory activities. These results also suggest that SLD sulfone could be a potent lead compound for AR inhibition in vivo. The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase.,Zheng X, Zhang L, Zhai J, Chen Y, Luo H, Hu X FEBS Lett. 2012 Jan 2;586(1):55-9. Epub 2011 Dec 8. PMID:22155003[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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