1x97: Difference between revisions

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-[[Image:1x97.gif|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1x97", creates the "Structure Box" on the page.
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-{{STRUCTURE_1x97|  PDB=1x97  |  SCENE=  }}
-'''Crystal structure of Aldose Reductase complexed with 2R4S (Stereoisomer of Fidarestat, 2S4S)'''
+==Crystal structure of Aldose Reductase complexed with 2R4S (Stereoisomer of Fidarestat, 2S4S)==
+<StructureSection load='1x97' size='340' side='right'caption='[[1x97]], [[Resolution|resolution]] 1.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1x97]] 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=1X97 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1X97 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]] 1.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FIR:(2R,4S)-2-AMINOFORMYL-6-FLUORO-SPIRO[CHROMAN-4,4-IMIDAZOLIDINE]-2,5-DIONE'>FIR</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=1x97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x97 OCA], [https://pdbe.org/1x97 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1x97 RCSB], [https://www.ebi.ac.uk/pdbsum/1x97 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1x97 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/x9/1x97_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=1x97 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Structure 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.
-==Overview==
+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<ref>PMID:15317464</ref>
-Structure 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.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-X97 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X97 OCA].
+</div>
+<div class="pdbe-citations 1x97" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-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:[http://www.ncbi.nlm.nih.gov/pubmed/15317464 15317464]
+*[[Aldose reductase 3D structures|Aldose reductase 3D structures]]
-[[Category: Aldehyde reductase]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Darmanin, C.]]
+[[Category: Darmanin C]]
-[[Category: El-Kabbani, O.]]
+[[Category: El-Kabbani O]]
-[[Category: Hazemann, I.]]
+[[Category: Hazemann I]]
-[[Category: Mitschler, A.]]
+[[Category: Mitschler A]]
-[[Category: Oka, M.]]
+[[Category: Oka M]]
-[[Category: Podjarny, A.]]
+[[Category: Podjarny A]]
-[[Category: Schulze-Briese, C.]]
+[[Category: Schulze-Briese C]]
-[[Category: Tomizaki, T.]]
+[[Category: Tomizaki T]]
-[[Category: Active site]]
-[[Category: Eight strandard alpha/beta barrel]]
-[[Category: The c-terminal end of the barrel]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 14:43:49 2008''