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1ag8

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[[Image:1ag8.gif|left|200px]]
 
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==ALDEHYDE DEHYDROGENASE FROM BOVINE MITOCHONDRIA==
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The line below this paragraph, containing "STRUCTURE_1ag8", creates the "Structure Box" on the page.
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<StructureSection load='1ag8' size='340' side='right'caption='[[1ag8]], [[Resolution|resolution]] 2.65&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'>[[1ag8]] 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=1AG8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1AG8 FirstGlance]. <br>
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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]] 2.65&#8491;</td></tr>
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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=1ag8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ag8 OCA], [https://pdbe.org/1ag8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ag8 RCSB], [https://www.ebi.ac.uk/pdbsum/1ag8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ag8 ProSAT]</span></td></tr>
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{{STRUCTURE_1ag8| PDB=1ag8 | SCENE= }}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ALDH2_BOVIN ALDH2_BOVIN]
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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/ag/1ag8_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=1ag8 ConSurf].
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<div style="clear:both"></div>
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'''ALDEHYDE DEHYDROGENASE FROM BOVINE MITOCHONDRIA'''
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==See Also==
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*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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.
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==About this Structure==
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1AG8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1AG8 OCA].
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==Reference==
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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://www.ncbi.nlm.nih.gov/pubmed/9195888 9195888]
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[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Hurley, T D.]]
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[[Category: Hurley TD]]
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[[Category: Steinmetz, C G.]]
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[[Category: Steinmetz CG]]
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[[Category: Alcohol metabolism]]
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[[Category: Aldehyde oxidation]]
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[[Category: Alpha/beta domain]]
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[[Category: Dehydrogenase]]
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[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 10:13:42 2008''
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Current revision

ALDEHYDE DEHYDROGENASE FROM BOVINE MITOCHONDRIA

PDB ID 1ag8

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