1ah4: Difference between revisions

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[[Image:1ah4.gif|left|200px]]


{{Structure
==PIG ALDOSE REDUCTASE, HOLO FORM==
|PDB= 1ah4 |SIZE=350|CAPTION= <scene name='initialview01'>1ah4</scene>, resolution 2.0&Aring;
<StructureSection load='1ah4' size='340' side='right'caption='[[1ah4]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
|SITE=  
== Structural highlights ==
|LIGAND= <scene name='pdbligand=NAP:NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE'>NAP</scene>
<table><tr><td colspan='2'>[[1ah4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AH4 FirstGlance]. <br>
|ACTIVITY= [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]  
</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&#8491;</td></tr>
|GENE=  
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AYA:N-ACETYLALANINE'>AYA</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=1ah4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ah4 OCA], [https://pdbe.org/1ah4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ah4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ah4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ah4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ALDR_PIG ALDR_PIG] 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/ah/1ah4_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=1ah4 ConSurf].
<div style="clear:both"></div>


'''PIG ALDOSE REDUCTASE, HOLO FORM'''
==See Also==
 
*[[Aldose reductase 3D structures|Aldose reductase 3D structures]]
 
*[[Heat Shock Protein structures|Heat Shock Protein structures]]
==Overview==
__TOC__
BACKGROUND: Aldose reductase (AR) is an NADPH-dependent enzyme implicated in long-term diabetic complications. Buried at the bottom of a deep hydrophobic cleft, the NADPH coenzyme is surrounded by the conserved hydrophilic residues of the AR active site. The existence of an anionic binding site near the NADP+ has been determined from the structures of the complexes of AR with citrate, cacodylate and glucose-6-phosphate. The inhibitor zopolrestat binds to this anionic site, and in the hydrophobic cleft, after a change of conformation which opens a 'specificity' pocket. RESULTS: The crystal structures of the porcine AR holoenzyme and its complexes with the inhibitors tolrestat and sorbinil have been solved; these structures are important as tolrestat and sorbinil are, pharmaceutically, the most well-studied AR inhibitors. The active site of the holoenzyme was analyzed, and binding of the inhibitors was found to involve two contact zones in the active site: first, a recognition region for hydrogen-bond acceptors near the coenzyme, with three centers, including the anionic site; and second, a hydrophobic contact zone in the active-site cleft, which in the case of tolrestat includes the specificity pocket. The conformational change leading to the opening of the specificity pocket upon tolrestat binding is different to the one seen upon zopolrestat binding; this pocket binds inhibitors that are more effective against AR than against aldehyde reductase. CONCLUSIONS: The active site of AR adapts itself to bind tightly to different inhibitors; this happens both upon binding to the inhibitor's hydrophilic heads, and at the hydrophobic and specificity pockets of AR, which can change their shape through different conformational changes of the same residues. This flexibility could explain the large variety of possible substrates of AR.
</StructureSection>
 
[[Category: Large Structures]]
==About this Structure==
1AH4 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AH4 OCA].
 
==Reference==
A 'specificity' pocket inferred from the crystal structures of the complexes of aldose reductase with the pharmaceutically important inhibitors tolrestat and sorbinil., Urzhumtsev A, Tete-Favier F, Mitschler A, Barbanton J, Barth P, Urzhumtseva L, Biellmann JF, Podjarny A, Moras D, Structure. 1997 May 15;5(5):601-12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9195881 9195881]
[[Category: Aldehyde reductase]]
[[Category: Single protein]]
[[Category: Sus scrofa]]
[[Category: Sus scrofa]]
[[Category: Moras, D.]]
[[Category: Moras D]]
[[Category: Podjarny, A.]]
[[Category: Podjarny A]]
[[Category: NAP]]
[[Category: aldose reductase]]
[[Category: diabetes]]
[[Category: inhibition]]
[[Category: oxidoreductase]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 09:57:27 2008''

Latest revision as of 18:24, 13 March 2024

PIG ALDOSE REDUCTASE, HOLO FORMPIG ALDOSE REDUCTASE, HOLO FORM

Structural highlights

1ah4 is a 1 chain structure with sequence from Sus scrofa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ALDR_PIG 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

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

1ah4, resolution 2.00Å

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