2ipw: Difference between revisions
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<StructureSection load='2ipw' size='340' side='right'caption='[[2ipw]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='2ipw' size='340' side='right'caption='[[2ipw]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2ipw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2ipw]] 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=2IPW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IPW FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2CL:(2,6-DICHLOROPHENYL)ACETIC+ACID'>2CL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | |||
<tr id=' | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ipw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ipw OCA], [https://pdbe.org/2ipw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ipw RCSB], [https://www.ebi.ac.uk/pdbsum/2ipw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ipw 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=2ipw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ipw OCA], [https://pdbe.org/2ipw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ipw RCSB], [https://www.ebi.ac.uk/pdbsum/2ipw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ipw 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]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Brownlee | [[Category: Brownlee JM]] | ||
[[Category: Harrison | [[Category: Harrison DHT]] | ||
[[Category: Pape | [[Category: Pape E]] | ||
Latest revision as of 13:14, 30 August 2023
Crystal Structure of C298A W219Y Aldose Reductase complexed with Dichlorophenylacetic acidCrystal Structure of C298A W219Y Aldose Reductase complexed with Dichlorophenylacetic acid
Structural highlights
FunctionALDR_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 PubMedThe competitive inhibition constants of series of inhibitors related to phenylacetic acid against both wild-type and the doubly mutanted C298A/W219Y aldose reductase have been measured. Van't Hoff analysis shows that these acids bind with an enthalpy near -6.8 kcal/mol derived from the electrostatic interactions, while the 100-fold differences in binding affinity appear to be largely due to entropic factors that result from differences in conformational freedom in the unbound state. These temperature studies also point out the difference between substrate and inhibitor binding. X-ray crystallographic analysis of a few of these inhibitor complexes both confirms the importance of a previously described anion binding site and reveals the hydrophobic nature of the primary binding site and its general plasticity. Based on these results, N-glycylthiosuccinimides were synthesized to demonstrate their potential in studies that probe distal binding sites. Reduced alpha-lipoic acid, an anti-oxidant and therapeutic for diabetic complications, was shown to bind aldose reductase with a binding constant of 1 microM. Structural and thermodynamic studies of simple aldose reductase-inhibitor complexes.,Brownlee JM, Carlson E, Milne AC, Pape E, Harrison DH Bioorg Chem. 2006 Dec;34(6):424-44. Epub 2006 Nov 2. PMID:17083960[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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