1mar: Difference between revisions
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<StructureSection load='1mar' size='340' side='right'caption='[[1mar]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='1mar' size='340' side='right'caption='[[1mar]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1mar]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[1mar]] 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=1MAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MAR 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=ZST:3,4-DIHYDRO-4-OXO-3-((5-TRIFLUOROMETHYL-2-BENZOTHIAZOLYL)METHYL)-1-PHTHALAZINE+ACETIC+ACID'>ZST</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=ZST:3,4-DIHYDRO-4-OXO-3-((5-TRIFLUOROMETHYL-2-BENZOTHIAZOLYL)METHYL)-1-PHTHALAZINE+ACETIC+ACID'>ZST</scene></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=1mar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mar OCA], [https://pdbe.org/1mar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mar RCSB], [https://www.ebi.ac.uk/pdbsum/1mar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mar 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 12:25, 5 May 2021
REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTATREFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT
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 PubMedAs the action of aldose reductase (EC 1.1.1.21) is believed to be linked to the pathogenesis of diabetic complications affecting the nervous, renal, and visual systems, the development of therapeutic agents has attracted intense effort. We report the refined 1.8 A x-ray structure of the human holoenzyme complexed with zopolrestat, one of the most potent noncompetitive inhibitors. The zopolrestat fits snugly in the hydrophobic active site pocket and induces a hinge-flap motion of two peptide segments that closes the pocket. Excellent complementarity and affinity are achieved on inhibitor binding by the formation of 110 contacts (< or = 4 A) with 15 residues (10 hydrophobic), 13 with the NADPH coenzyme and 9 with four water molecules. The structure is key to understanding the mode of action of this class of inhibitors and for rational design of better therapeutics. Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat.,Wilson DK, Tarle I, Petrash JM, Quiocho FA Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9847-51. PMID:8234324[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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