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1a4z

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ALDEHYDE DEHYDROGENASE FROM BOVINE MITOCHONDRIA COMPLEX WITH NAD (REDUCED) AND SAMARIUM (III)

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Retrieved from "http://52.214.119.220/wiki/index.php/1a4z"

Categories: Bos taurus | Large Structures | Hurley TD | Steinmetz CG

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-[[Image:1a4z.gif|left|200px]]<br /><applet load="1a4z" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="1a4z, resolution 2.75&Aring;" />
-'''ALDEHYDE DEHYDROGENASE FROM BOVINE MITOCHONDRIA COMPLEX WITH NAD (REDUCED) AND SAMARIUM (III)'''<br />
-==Overview==
+==ALDEHYDE DEHYDROGENASE FROM BOVINE MITOCHONDRIA COMPLEX WITH NAD (REDUCED) AND SAMARIUM (III)==
-BACKGROUND: The single genetic factor most strongly correlated with, reduced alcohol consumption and incidence of alcoholism is a naturally, occurring variant of mitochondrial aldehyde dehydrogenase (ALDH2). This, variant contains a glutamate to lysine substitution at position 487, (E487K). The E487K variant of ALDH2 is found in approximately 50% of the, Asian population, and is associated with a phenotypic loss of ALDH2, activity in both heterozygotes and homozygotes. ALDH2-deficient, individuals exhibit an averse response to ethanol consumption, which is, probably caused by elevated levels of blood acetaldehyde. The structure of, ALDH2 is important for the elucidation of its catalytic mechanism, to gain, a clear understanding of the contribution of ALDH2 to the genetic, component of alcoholism and for the development of specific ALDH2, inhibitors as potential drugs for use in the treatment of alcoholism., RESULTS: The X-ray structure of bovine ALDH2 has been solved to 2.65 A in, its free form and to 2.75 A in a complex with NAD+. The enzyme structure, contains three domains; two dinucleotide-binding domains and a small, three-stranded beta-sheet domain, which is involved in subunit, interactions in this tetrameric enzyme. The E487K mutation occurs in this, small oligomerization domain and is located at a key interface between, subunits immediately below the active site of another monomer. The active, site of ALDH2 is divided into two halves by the nicotinamide ring of NAD+., Adjacent to the A-side (Pro-R) of the nicotinamide ring is a cluster of, three cysteines (Cys301, Cys302 and Cys303) and adjacent to the B-side, (Pro-S) are Thr244, Glu268, Glu476 and an ordered water molecule bound to, Thr244 and Glu476. CONCLUSIONS: Although there is a recognizable, Rossmann-type fold, the coenzyme-binding region of ALDH2 binds NAD+ in a, manner not seen in other NAD+-binding enzymes. The positions of the, residues near the nicotinamide ring of NAD+ suggest a chemical mechanism, whereby Glu268 functions as a general base through a bound water molecule., The sidechain amide nitrogen of Asn169 and the peptide nitrogen of Cys302, are in position to stabilize the oxyanion present in the tetrahedral, transition state prior to hydride transfer. The functional importance of, residue Glu487 now appears to be due to indirect interactions of this, residue with the substrate-binding site via Arg264 and Arg475.
+<StructureSection load='1a4z' size='340' side='right'caption='[[1a4z]], [[Resolution|resolution]] 2.75&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1a4z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A4Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1A4Z 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]] 2.75&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SM:SAMARIUM+(III)+ION'>SM</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=1a4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a4z OCA], [https://pdbe.org/1a4z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1a4z RCSB], [https://www.ebi.ac.uk/pdbsum/1a4z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1a4z ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/ALDH2_BOVIN ALDH2_BOVIN]
+== 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/a4/1a4z_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=1a4z ConSurf].
+<div style="clear:both"></div>
-==About this Structure==
+==See Also==
-A4Z is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] with SM and NAD as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Aldehyde_dehydrogenase_(NAD(+)) Aldehyde dehydrogenase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.3 1.2.1.3] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1A4Z OCA].
+*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
+__TOC__
-==Reference==
+</StructureSection>
-Structure of mitochondrial aldehyde dehydrogenase: the genetic component of ethanol aversion., Steinmetz CG, Xie P, Weiner H, Hurley TD, Structure. 1997 May 15;5(5):701-11. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9195888 9195888]
-[[Category: Aldehyde dehydrogenase (NAD(+))]]
 [[Category: Bos taurus]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Hurley, T.D.]]
+[[Category: Hurley TD]]
-[[Category: Steinmetz, C.G.]]
+[[Category: Steinmetz CG]]
-[[Category: NAD]]
-[[Category: SM]]
-[[Category: alcohol metabolism]]
-[[Category: aldehyde oxidation]]
-[[Category: alpha/beta domain]]
-[[Category: dehydrogenase]]
-[[Category: oxidoreductase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 10:36:42 2007''

1a4z

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ALDEHYDE DEHYDROGENASE FROM BOVINE MITOCHONDRIA COMPLEX WITH NAD (REDUCED) AND SAMARIUM (III)

Structural highlights

Function

Evolutionary Conservation

See Also

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