1mar: Difference between revisions

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New page: left|200px<br /> <applet load="1mar" size="450" color="white" frame="true" align="right" spinBox="true" caption="1mar, resolution 1.8Å" /> '''REFINED 1.8 ANGSTROM...
 
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[[Image:1mar.gif|left|200px]]<br />
<applet load="1mar" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1mar, resolution 1.8&Aring;" />
'''REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT'''<br />


==Overview==
==REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT==
As the action of aldose reductase (EC 1.1.1.21) is believed to be linked, to the pathogenesis of diabetic complications affecting the nervous, renal, and visual systems, the development of therapeutic agents has, attracted intense effort. We report the refined 1.8 A x-ray structure of, the human holoenzyme complexed with zopolrestat, one of the most potent, noncompetitive inhibitors. The zopolrestat fits snugly in the hydrophobic, active site pocket and induces a hinge-flap motion of two peptide segments, that closes the pocket. Excellent complementarity and affinity are, achieved on inhibitor binding by the formation of 110 contacts (&lt; or = 4, A) with 15 residues (10 hydrophobic), 13 with the NADPH coenzyme and 9, with four water molecules. The structure is key to understanding the mode, of action of this class of inhibitors and for rational design of better, therapeutics.
<StructureSection load='1mar' size='340' side='right'caption='[[1mar]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1mar]] 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=1MAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MAR 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=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=ZST:3,4-DIHYDRO-4-OXO-3-((5-TRIFLUOROMETHYL-2-BENZOTHIAZOLYL)METHYL)-1-PHTHALAZINE+ACETIC+ACID'>ZST</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=1mar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mar OCA], [https://pdbe.org/1mar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mar RCSB], [https://www.ebi.ac.uk/pdbsum/1mar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mar 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/ma/1mar_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=1mar ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1MAR 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 ZST 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=1MAR OCA].
*[[Aldose reductase 3D structures|Aldose reductase 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Refined 1.8 A structure of human aldose reductase complexed with the potent inhibitor zopolrestat., Wilson DK, Tarle I, Petrash JM, Quiocho FA, Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9847-51. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8234324 8234324]
[[Category: Aldehyde reductase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Quiocho, F.A.]]
[[Category: Quiocho FA]]
[[Category: Wilson, D.K.]]
[[Category: Wilson DK]]
[[Category: NAP]]
[[Category: ZST]]
[[Category: oxidoreductase(nadp)]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:09:42 2007''

Latest revision as of 10:42, 14 February 2024

REFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTATREFINED 1.8 ANGSTROMS STRUCTURE OF HUMAN ALDOSE REDUCTASE COMPLEXED WITH THE POTENT INHIBITOR ZOPOLRESTAT

Structural highlights

1mar is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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

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

See Also

1mar, resolution 1.80Å

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