1x98: Difference between revisions
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<StructureSection load='1x98' size='340' side='right'caption='[[1x98]], [[Resolution|resolution]] 1.30Å' scene=''> | <StructureSection load='1x98' size='340' side='right'caption='[[1x98]], [[Resolution|resolution]] 1.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1x98]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1x98]] 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=1X98 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X98 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=FIS:(2S,4R)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4-IMIDAZOLIDINE]-2,5-DIONE'>FIS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=FIS:(2S,4R)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4-IMIDAZOLIDINE]-2,5-DIONE'>FIS</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1pwm|1pwm]], [[1x96|1x96]], [[1x97|1x97]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1pwm|1pwm]], [[1x96|1x96]], [[1x97|1x97]]</div></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=1x98 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x98 OCA], [https://pdbe.org/1x98 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x98 RCSB], [https://www.ebi.ac.uk/pdbsum/1x98 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x98 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. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Revision as of 19:34, 27 October 2021
Crystal structure of Aldose Reductase complexed with 2S4R (Stereoisomer of Fidarestat, 2S4S)Crystal structure of Aldose Reductase complexed with 2S4R (Stereoisomer of Fidarestat, 2S4S)
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 PubMedStructure determinations of human aldose reductase holoenzyme in complex with the 2S4R-,2R4S- and 2R4R-isomers of the potent inhibitor Fidarestat ((2S,4S)-6-fluoro-2',5'-dioxospiro[chroman-4,4'-imidazoline]-2-carboxamide ) were carried out in order to elucidate the binding modes responsible for the differences in their inhibitory potencies. In the complex structure with the 2R4S-isomer the cyclic imide moiety formed hydrogen bonds with the side-chains of Trp111, Tyr48 and His110. In the attempt to determine the complex structure with the least potent 2R4R-isomer this ligand was not observed, and instead, the active site was simultaneously occupied by two citrate molecules (occupancies of 60% and 40%). In the case of 2S4R, the active site was occupied by a citrate molecule which anchors the 2S4R-isomer from its carbamoyl group. The structures of the complexes suggest that the differences in the interactions between the cyclic imide rings and carbamoyl groups of the compounds with residues His110, Trp111, Trp219 and Cys298 account for differences in their inhibitory potencies. High-resolution structures of human aldose reductase holoenzyme in complex with stereoisomers of the potent inhibitor Fidarestat: stereospecific interaction between the enzyme and a cyclic imide type inhibitor.,El-Kabbani O, Darmanin C, Oka M, Schulze-Briese C, Tomizaki T, Hazemann I, Mitschler A, Podjarny A J Med Chem. 2004 Aug 26;47(18):4530-7. PMID:15317464[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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