View source for 1b15


==ALCOHOL DEHYDROGENASE FROM DROSOPHILA LEBANONENSIS TERNARY COMPLEX WITH NAD-ACETONE==
<StructureSection load='1b15' size='340' side='right'caption='[[1b15]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1b15]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Scaptodrosophila_lebanonensis Scaptodrosophila lebanonensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B15 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1B15 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAE:NICOTINAMIDE+ADENINE+DINUCLEOTIDE+ACETONE+ADDUCT'>NAE</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1b14|1b14]], [[1b2l|1b2l]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alcohol_dehydrogenase Alcohol dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.1 1.1.1.1] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1b15 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b15 OCA], [http://pdbe.org/1b15 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1b15 RCSB], [http://www.ebi.ac.uk/pdbsum/1b15 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1b15 ProSAT]</span></td></tr>
</table>
== 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/b1/1b15_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=1b15 ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Drosophila alcohol dehydrogenase (DADH) is an NAD+-dependent enzyme that catalyzes the oxidation of alcohols to aldehydes/ketones. DADH is the member of the short-chain dehydrogenases/reductases family (SDR) for which the largest amount of biochemical data has been gathered during the last three decades. The crystal structures of one binary form (NAD+) and three ternary complexes with NAD+.acetone, NAD+.3-pentanone and NAD+.cyclohexanone were solved at 2.4, 2.2, 1. 4 and 1.6 A resolution, respectively. From the molecular interactions observed, the reaction mechanism could be inferred. The structure of DADH undergoes a conformational change in order to bind the coenzyme. Furthermore, upon binding of the ketone, a region that was disordered in the apo form (186-191) gets stabilized and closes the active site cavity by creating either a small helix (NAD+. acetone, NAD+.3-pentanone) or an ordered loop (NAD+.cyclohexanone). The active site pocket comprises a hydrophobic bifurcated cavity which explains why the enzyme is more efficient in oxidizing secondary aliphatic alcohols (preferably R form) than primary ones. Difference Fourier maps showed that the ketone inhibitor molecule has undergone a covalent reaction with the coenzyme in all three ternary complexes. Due to the presence of the positively charged ring of the coenzyme (NAD+) and the residue Lys155, the amino acid Tyr151 is in its deprotonated (tyrosinate) state at physiological pH. Tyr151 can subtract a proton from the enolic form of the ketone and catalyze a nucleophilic attack of the Calphaatom to the C4 position of the coenzyme creating an NAD-ketone adduct. The binding of these NAD-ketone adducts to DADH accounts for the inactivation of the enzyme. The catalytic reaction proceeds in a similar way, involving the same amino acids as in the formation of the NAD-ketone adduct. The p Kavalue of 9-9.5 obtained by kinetic measurements on apo DADH can be assigned to a protonated Tyr151 which is converted to an unprotonated tyrosinate (p Ka7.6) by the influence of the positively charged nicotinamide ring in the binary enzyme-NAD+form. pH independence during the release of NADH from the binary complex enzyme-NADH can be explained by either a lack of electrostatic interaction between the coenzyme and Tyr151 or an apparent p Kavalue for this residue higher than 10.0.

The catalytic reaction and inhibition mechanism of Drosophila alcohol dehydrogenase: observation of an enzyme-bound NAD-ketone adduct at 1.4 A resolution by X-ray crystallography.,Benach J, Atrian S, Gonzalez-Duarte R, Ladenstein R J Mol Biol. 1999 Jun 4;289(2):335-55. PMID:10366509<ref>PMID:10366509</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1b15" style="background-color:#fffaf0;"></div>

==See Also==
*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Alcohol dehydrogenase]]
[[Category: Large Structures]]
[[Category: Scaptodrosophila lebanonensis]]
[[Category: Atrian, S]]
[[Category: Benach, J]]
[[Category: Gonzalez-Duarte, R]]
[[Category: Ladenstein, R]]
[[Category: Detoxification]]
[[Category: Drosophila lebanonensis]]
[[Category: Metabolism]]
[[Category: Nad- acetone adduct]]
[[Category: Oxidoreductase]]
[[Category: Short-chain dehydrogenases/reductase]]
[[Category: Ternary complex]]