1t41

<StructureSection load='1t41' size='340' side='right' caption='[[1t41]], [[Resolution|resolution]] 1.05&Aring;' scene=''>

<table><tr><td colspan='2'>[[1t41]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T41 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1T41 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ID5:[5-FLUORO-2-({[(4,5,7-TRIFLUORO-1,3-BENZOTHIAZOL-2-YL)METHYL]AMINO}CARBONYL)PHENOXY]ACETIC+ACID'>ID5</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_reductase Aldehyde reductase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t41 OCA], [http://pdbe.org/1t41 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1t41 RCSB], [http://www.ebi.ac.uk/pdbsum/1t41 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1t41 ProSAT]</span></td></tr>

[[http://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.

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t4/1t41_consurf.spt"</scriptWhenChecked>

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== Publication Abstract from PubMed ==

The X-ray crystal structure of human aldose reductase (ALR2) in complex with the inhibitor IDD552 was determined using crystals obtained from two crystallization conditions with different pH values (pH 5 and 8). In both structures the charged carboxylic head of the inhibitor binds to the active site, making hydrogen-bond interactions with His110 and Tyr48 and electrostatic interactions with NADP+. There is an important difference between the two structures: the observation of a double conformation of the carboxylic acid moiety of the inhibitor at pH 8, with one water molecule interacting with the main configuration. This is the first time that a water molecule has been observed deep inside the ALR2 active site. Furthermore, in the configuration with the lower occupancy factor the difference electron-density map shows a clear peak (2.5sigma) for the H atom in the hydrogen bond between the inhibitor's carboxylic acid and the Tyr48 side-chain O atom. The position of this peak implies that this H atom is shared between both O atoms, indicating possible direct proton transfer from this residue to the inhibitor. This fact agrees with the model of the catalytic mechanism, in which the proton is donated by the Tyr48 hydroxyl to the substrate. These observations are useful both in drug design and in understanding the ALR2 mechanism.

 

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== References ==

[[Category: Aldehyde reductase]]

[[Category: Human]]

[[Category: Chevrier, B]]

[[Category: Hazemann, I]]

[[Category: Joachimiak, A]]

[[Category: Karplus, M]]

[[Category: Mitschler, A]]

[[Category: Podjarny, A]]

[[Category: Ruiz, F]]

[[Category: Schneider, T]]

[[Category: Ternary complex]]