1z3n

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[[Image:1z3n.gif|left|200px]]
 
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==Human aldose reductase in complex with NADP+ and the inhibitor lidorestat at 1.04 angstrom==
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The line below this paragraph, containing "STRUCTURE_1z3n", creates the "Structure Box" on the page.
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<StructureSection load='1z3n' size='340' side='right'caption='[[1z3n]], [[Resolution|resolution]] 1.04&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'>[[1z3n]] 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=1Z3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Z3N 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]] 1.04&#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=3NA:{3-[(4,5,7-TRIFLUORO-1,3-BENZOTHIAZOL-2-YL)METHYL]-1H-INDOL-1-YL}ACETIC+ACID'>3NA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr>
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{{STRUCTURE_1z3n| PDB=1z3n | 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=1z3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1z3n OCA], [https://pdbe.org/1z3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1z3n RCSB], [https://www.ebi.ac.uk/pdbsum/1z3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1z3n 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/z3/1z3n_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=1z3n ConSurf].
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<div style="clear:both"></div>
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'''Human aldose reductase in complex with NADP+ and the inhibitor lidorestat at 1.04 angstrom'''
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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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Recent efforts to identify treatments for chronic diabetic complications have resulted in the discovery of a novel series of highly potent and selective 3-[(benzothiazol-2-yl)methyl]indole-N-alkanoic acid aldose reductase inhibitors. The lead candidate, 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat, 9) inhibits aldose reductase with an IC(50) of 5 nM, while being 5400 times less active against aldehyde reductase, a related enzyme involved in the detoxification of reactive aldehydes. It lowers nerve and lens sorbitol levels with ED(50)'s of 1.9 and 4.5 mg/kg/d po, respectively, in the 5-day STZ-induced diabetic rat model. In a 3-month diabetic intervention model (1 month of diabetes followed by 2 months of drug treatment at 5 mg/kg/d po), it normalizes polyols and reduces the motor nerve conduction velocity deficit by 59% relative to diabetic controls. It has a favorable pharmacokinetic profile (F, 82%; t(1/2), 5.6 h; Vd, 0.694 L/kg) with good drug penetration in target tissues (C(max) in sciatic nerve and eye are 2.36 and 1.45 mug equiv/g, respectively, when dosed with [(14)C]lidorestat at 10 mg/kg po).
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==About this Structure==
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1Z3N 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=1Z3N OCA].
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==Reference==
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Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications., Van Zandt MC, Jones ML, Gunn DE, Geraci LS, Jones JH, Sawicki DR, Sredy J, Jacot JL, Dicioccio AT, Petrova T, Mitschler A, Podjarny AD, J Med Chem. 2005 May 5;48(9):3141-52. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15857120 15857120]
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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: Dicioccio, A T.]]
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[[Category: Dicioccio AT]]
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[[Category: Geraci, L S.]]
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[[Category: Geraci LS]]
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[[Category: Gunn, D E.]]
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[[Category: Gunn DE]]
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[[Category: Jacot, J L.]]
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[[Category: Jacot JL]]
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[[Category: Jones, J H.]]
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[[Category: Jones JH]]
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[[Category: Jones, M L.]]
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[[Category: Jones ML]]
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[[Category: Mitschler, A.]]
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[[Category: Mitschler A]]
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[[Category: Petrova, T.]]
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[[Category: Petrova T]]
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[[Category: Podjarny, A D.]]
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[[Category: Podjarny AD]]
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[[Category: Sawicki, D R.]]
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[[Category: Sawicki DR]]
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[[Category: Sredy, J.]]
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[[Category: Sredy J]]
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[[Category: Zandt, M C.Van.]]
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[[Category: Van Zandt MC]]
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[[Category: Lidorestat]]
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[[Category: Nadp+]]
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[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:08:41 2008''
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Current revision

Human aldose reductase in complex with NADP+ and the inhibitor lidorestat at 1.04 angstrom

PDB ID 1z3n

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