2acr

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[[Image:2acr.jpg|left|200px]]
 
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==AN ANION BINDING SITE IN HUMAN ALDOSE REDUCTASE: MECHANISTIC IMPLICATIONS FOR THE BINDING OF CITRATE, CACODYLATE, AND GLUCOSE-6-PHOSPHATE==
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The line below this paragraph, containing "STRUCTURE_2acr", creates the "Structure Box" on the page.
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<StructureSection load='2acr' size='340' side='right'caption='[[2acr]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2acr]] 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=2ACR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ACR FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.76&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>
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{{STRUCTURE_2acr| PDB=2acr | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2acr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2acr OCA], [https://pdbe.org/2acr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2acr RCSB], [https://www.ebi.ac.uk/pdbsum/2acr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2acr ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ac/2acr_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2acr ConSurf].
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<div style="clear:both"></div>
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'''AN ANION BINDING SITE IN HUMAN ALDOSE REDUCTASE: MECHANISTIC IMPLICATIONS FOR THE BINDING OF CITRATE, CACODYLATE, AND GLUCOSE-6-PHOSPHATE'''
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==See Also==
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*[[Aldose reductase 3D structures|Aldose reductase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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Aldose reductase is a NADPH-dependent aldo-keto reductase involved in the pathogenesis of some diabetic and galactosemic complications. The published crystal structure of human aldose reductase [Wilson et al. (1992) Science 257, 81-84] contains a hitherto unexplained electron density positioned within the active site pocket facing the nicotinamide ring of the NADPH and other key active site residues (Tyr48, His110, and Cys298). In this paper we identify the electron density as citrate, which is present in the crystallization buffer (pH 5.0), and provide confirmatory evidence by both kinetic and crystallographic experiments. Citrate is an uncompetitive inhibitor in the forward reaction with respect to aldehyde (reduction of aldehyde), while it is a competitive inhibitor with respect to alcohol in the backward reaction (oxidation of alcohol), indicating that it interacts with the enzyme-NADP(+)-product complex. Citrate can be replaced in the crystalline enzyme complex by cacodylate or glucose 6-phosphate; the structure of each of these complexes shows the specific molecule bound in the active site. All of the structures have been determined to a nominal resolution of 1.76 A and refined to R-factors below 18%. While cacodylate can be bound within the active site under the crystallization conditions, it does not inhibit the wild-type enzyme in solution. Glucose 6-phosphate, however, is a substrate for aldose reductase. The similar location of the negative charges of citrate, cacodylate, and glucose 6-phosphate within the active site suggests an anion-binding site delineated by the C4N of nicotinamide, the OH of Tyr48, and the N epsilon of His110. The location of citrate binding in the active site leads to a plausible catalytic mechanism for aldose reductase.
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==About this Structure==
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2ACR 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=2ACR OCA].
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==Reference==
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An anion binding site in human aldose reductase: mechanistic implications for the binding of citrate, cacodylate, and glucose 6-phosphate., Harrison DH, Bohren KM, Ringe D, Petsko GA, Gabbay KH, Biochemistry. 1994 Mar 1;33(8):2011-20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/8117658 8117658]
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[[Category: Aldehyde reductase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Bohren, K M.]]
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[[Category: Bohren KM]]
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[[Category: Gabbay, K H.]]
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[[Category: Gabbay KH]]
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[[Category: Harrison, D H.]]
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[[Category: Harrison DH]]
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[[Category: Petsko, G A.]]
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[[Category: Petsko GA]]
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[[Category: Ringe, D.]]
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[[Category: Ringe D]]
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[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:53:12 2008''
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Current revision

AN ANION BINDING SITE IN HUMAN ALDOSE REDUCTASE: MECHANISTIC IMPLICATIONS FOR THE BINDING OF CITRATE, CACODYLATE, AND GLUCOSE-6-PHOSPHATE

PDB ID 2acr

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