1t40: Difference between revisions

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New page: left|200px<br /> <applet load="1t40" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t40, resolution 1.80Å" /> '''Crystal structure o...
 
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[[Image:1t40.gif|left|200px]]<br />
<applet load="1t40" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1t40, resolution 1.80&Aring;" />
'''Crystal structure of human aldose reductase complexed with NADP and IDD552 at ph 5'''<br />


==Overview==
==Crystal structure of human aldose reductase complexed with NADP and IDD552 at ph 5==
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.
<StructureSection load='1t40' size='340' side='right'caption='[[1t40]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1t40]] 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=1T40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1T40 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1t40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t40 OCA], [https://pdbe.org/1t40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1t40 RCSB], [https://www.ebi.ac.uk/pdbsum/1t40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1t40 ProSAT]</span></td></tr>
</table>
== 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 ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/t4/1t40_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=1t40 ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1T40 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 NAP and ID5 as [http://en.wikipedia.org/wiki/ligands ligands]. 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=1T40 OCA].
*[[Aldose reductase 3D structures|Aldose reductase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
The crystallographic structure of the aldose reductase-IDD552 complex shows direct proton donation from tyrosine 48., Ruiz F, Hazemann I, Mitschler A, Joachimiak A, Schneider T, Karplus M, Podjarny A, Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1347-54. Epub 2004, Jul 21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15272156 15272156]
[[Category: Aldehyde reductase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Chevrier, B.]]
[[Category: Chevrier B]]
[[Category: Hazemann, I.]]
[[Category: Hazemann I]]
[[Category: Joachimiak, A.]]
[[Category: Joachimiak A]]
[[Category: Karplus, M.]]
[[Category: Karplus M]]
[[Category: Mitschler, A.]]
[[Category: Mitschler A]]
[[Category: Podjarny, A.]]
[[Category: Podjarny A]]
[[Category: Ruiz, F.]]
[[Category: Ruiz F]]
[[Category: Schneider, T.]]
[[Category: Schneider T]]
[[Category: ID5]]
[[Category: NAP]]
[[Category: aldose reductase]]
[[Category: inhibitor binding]]
[[Category: ternary complex]]
[[Category: x-ray crystallography]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:20:13 2007''

Latest revision as of 13:30, 13 March 2024

Crystal structure of human aldose reductase complexed with NADP and IDD552 at ph 5

1t40, resolution 1.80Å

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