This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1ef3
From Proteopedia
(Difference between revisions)
| (17 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | [[Image:1ef3.jpg|left|200px]]<br /><applet load="1ef3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
| - | caption="1ef3, resolution 2.8Å" /> | ||
| - | '''FIDARESTAT BOUND TO HUMAN ALDOSE REDUCTASE'''<br /> | ||
| - | == | + | ==FIDARESTAT BOUND TO HUMAN ALDOSE REDUCTASE== |
| + | <StructureSection load='1ef3' size='340' side='right'caption='[[1ef3]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[1ef3]] is a 2 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=1EF3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EF3 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]] 2.8Å</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></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=1ef3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ef3 OCA], [https://pdbe.org/1ef3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ef3 RCSB], [https://www.ebi.ac.uk/pdbsum/1ef3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ef3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == 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 == | ||
| + | [[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/ef/1ef3_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=1ef3 ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
The absolute configuration of the aldose reductase (AR) inhibitor, (+)-(2S,4S)-6-fluoro-2',5'-dioxospiro inverted question markchroman-4, 4'-imidazolidine-2-carboxamide (fidarestat), was established indirectly by single-crystal X-ray analysis of (+)-(2S, 4S)-8-bromo-6-fluoro-2',5'-dioxospiro inverted question markchroman-4, 4'-imidazolidine-2-carboxylic acid (1). The crystal structure of human AR complexed with fidarestat was determined, and the specific inhibition activity was discussed on the basis of the three-dimensional interactions between them. The structure clarified that fidarestat was located in the active site by hydrophilic and hydrophobic interactions and that the carbamoyl group of fidarestat was a very effective substituent for affinity to AR and for selectivity between AR and aldehyde reductase (AHR). Explanations for the differences between the observed activities of fidarestat and its stereoisomer 2 were suggested by computer modeling. | The absolute configuration of the aldose reductase (AR) inhibitor, (+)-(2S,4S)-6-fluoro-2',5'-dioxospiro inverted question markchroman-4, 4'-imidazolidine-2-carboxamide (fidarestat), was established indirectly by single-crystal X-ray analysis of (+)-(2S, 4S)-8-bromo-6-fluoro-2',5'-dioxospiro inverted question markchroman-4, 4'-imidazolidine-2-carboxylic acid (1). The crystal structure of human AR complexed with fidarestat was determined, and the specific inhibition activity was discussed on the basis of the three-dimensional interactions between them. The structure clarified that fidarestat was located in the active site by hydrophilic and hydrophobic interactions and that the carbamoyl group of fidarestat was a very effective substituent for affinity to AR and for selectivity between AR and aldehyde reductase (AHR). Explanations for the differences between the observed activities of fidarestat and its stereoisomer 2 were suggested by computer modeling. | ||
| - | + | A potent aldose reductase inhibitor, (2S,4S)-6-fluoro-2', 5'-dioxospiro[chroman-4,4'-imidazolidine]-2-carboxamide (Fidarestat): its absolute configuration and interactions with the aldose reductase by X-ray crystallography.,Oka M, Matsumoto Y, Sugiyama S, Tsuruta N, Matsushima M J Med Chem. 2000 Jun 15;43(12):2479-83. PMID:10882376<ref>PMID:10882376</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 1ef3" style="background-color:#fffaf0;"></div> | |
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ||
| - | + | ==See Also== | |
| + | *[[Aldose reductase 3D structures|Aldose reductase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Matsumoto Y]] | ||
| + | [[Category: Matsushima M]] | ||
| + | [[Category: Oka M]] | ||
| + | [[Category: Sugiyama S]] | ||
| + | [[Category: Tsuruta N]] | ||
Current revision
FIDARESTAT BOUND TO HUMAN ALDOSE REDUCTASE
| |||||||||||
