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1abn

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(New page: 200px<br /> <applet load="1abn" size="450" color="white" frame="true" align="right" spinBox="true" caption="1abn, resolution 2.4&Aring;" /> '''THE CRYSTAL STRUCTUR...)
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[[Image:1abn.gif|left|200px]]<br />
 
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<applet load="1abn" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1abn, resolution 2.4&Aring;" />
 
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'''THE CRYSTAL STRUCTURE OF THE ALDOSE REDUCTASE NADPH BINARY COMPLEX'''<br />
 
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==Overview==
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==THE CRYSTAL STRUCTURE OF THE ALDOSE REDUCTASE NADPH BINARY COMPLEX==
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Aldose reductase is an NADPH-dependent oxidoreductase that catalyzes the, reduction of a broad range of aldehydes, including glucose. Since aldose, reductase has been strongly implicated in the development of the chronic, complications of diabetes mellitus, much effort has been devoted to, understanding the structure and mechanism of this enzyme, and many aldose, reductase inhibitors have been developed as potential drugs for the, treatment of these complications. We describe here the 2.75 A crystal, structure of recombinant human aldose reductase (Cys-298 to Ser mutant), complexed with NADPH. This mutant displays unusual kinetic behavior, characterized by high Km/high Vmax substrate kinetics and reduced, sensitivity to certain aldose reductase inhibitors. The crystal structure, revealed that the enzyme is a beta/alpha-barrel with the coenzyme-binding, domain located at the carboxyl-terminal end of the parallel strands of the, barrel. The enzyme undergoes a large conformational change upon binding, NADPH which involves the reorientation of loop 7 to a position which, appears to lock the coenzyme into place. NADPH is bound to aldose, reductase in an unusual manner, more similar to FAD- rather than, NAD(P)-dependent oxidoreductases. No disulfide bridges were observed in, the crystal structure.
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<StructureSection load='1abn' size='340' side='right'caption='[[1abn]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1abn]] 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=1ABN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ABN FirstGlance]. <br>
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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]] 2.4&#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=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
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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=1abn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1abn OCA], [https://pdbe.org/1abn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1abn RCSB], [https://www.ebi.ac.uk/pdbsum/1abn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1abn 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/ab/1abn_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=1abn ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1ABN is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NDP as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1ABN OCA].
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*[[Aldose reductase 3D structures|Aldose reductase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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The crystal structure of the aldose reductase.NADPH binary complex., Borhani DW, Harter TM, Petrash JM, J Biol Chem. 1992 Dec 5;267(34):24841-7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=1447221 1447221]
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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: Borhani, D.W.]]
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[[Category: Borhani DW]]
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[[Category: Harter, T.M.]]
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[[Category: Harter TM]]
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[[Category: Petrash, J.M.]]
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[[Category: Petrash JM]]
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[[Category: NDP]]
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[[Category: oxidoreductase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Thu Nov 8 12:33:26 2007''
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Current revision

THE CRYSTAL STRUCTURE OF THE ALDOSE REDUCTASE NADPH BINARY COMPLEX

PDB ID 1abn

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