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1ee2

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[[Image:1ee2.jpg|left|200px]]<br /><applet load="1ee2" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ee2, resolution 1.54&Aring;" />
 
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'''THE STRUCTURE OF STEROID-ACTIVE ALCOHOL DEHYDROGENASE AT 1.54 A RESOLUTION'''<br />
 
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==Overview==
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==THE STRUCTURE OF STEROID-ACTIVE ALCOHOL DEHYDROGENASE AT 1.54 A RESOLUTION==
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A structure determination in combination with a kinetic study of the steroid converting isozyme of horse liver alcohol dehydrogenase, SS-ADH, is presented. Kinetic parameters for the substrates, 5beta-androstane-3beta,17beta-ol, 5beta-androstane-17beta-ol-3-one, ethanol, and various secondary alcohols and the corresponding ketones are compared for the SS- and EE-isozymes which differ by nine amino acid substitutions and one deletion. Differences in substrate specificity and stereoselectivity are explained on the basis of individual kinetic rate constants for the underlying ordered bi-bi mechanism. SS-ADH was crystallized in complex with 3alpha,7alpha,12alpha-trihydroxy-5beta-cholan -24-acid (cholic acid) and NAD(+), but microspectrophotometric analysis of single crystals proved it to be a mixed complex containing 60-70% NAD(+) and 30-40% NADH. The crystals belong to the space group P2(1) with cell dimensions a = 55.0 A, b = 73.2 A, c = 92.5 A, and beta = 102.5 degrees. A 98% complete data set to 1.54-A resolution was collected at 100 K using synchrotron radiation. The structure was solved by the molecular replacement method utilizing EE-ADH as the search model. The major structural difference between the isozymes is a widening of the substrate channel. The largest shifts in C(alpha) carbon positions (about 5 A) are observed in the loop region, in which a deletion of Asp115 is found in the SS isozyme. SS-ADH easily accommodates cholic acid, whereas steroid substrates of similar bulkiness would not fit into the EE-ADH substrate site. In the ternary complex with NAD(+)/NADH, we find that the carboxyl group of cholic acid ligates to the active site zinc ion, which probably contributes to the strong binding in the ternary NAD(+) complex.
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<StructureSection load='1ee2' size='340' side='right'caption='[[1ee2]], [[Resolution|resolution]] 1.54&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ee2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Equus_caballus Equus caballus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EE2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EE2 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]] 1.54&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CHD:CHOLIC+ACID'>CHD</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=1ee2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ee2 OCA], [https://pdbe.org/1ee2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ee2 RCSB], [https://www.ebi.ac.uk/pdbsum/1ee2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ee2 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ADH1S_HORSE ADH1S_HORSE]
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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/ee/1ee2_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=1ee2 ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1EE2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=NAD:'>NAD</scene> and <scene name='pdbligand=CHD:'>CHD</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EE2 OCA].
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*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Structural basis for substrate specificity differences of horse liver alcohol dehydrogenase isozymes., Adolph HW, Zwart P, Meijers R, Hubatsch I, Kiefer M, Lamzin V, Cedergren-Zeppezauer E, Biochemistry. 2000 Oct 24;39(42):12885-97. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11041853 11041853]
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[[Category: Alcohol dehydrogenase]]
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[[Category: Equus caballus]]
[[Category: Equus caballus]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Adolph, H W.]]
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[[Category: Adolph HW]]
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[[Category: CHD]]
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[[Category: NAD]]
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[[Category: ZN]]
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[[Category: alcohol]]
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[[Category: dehydrogenase]]
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[[Category: nicotinamide coenzyme]]
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[[Category: steroid binding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:26:49 2008''
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Current revision

THE STRUCTURE OF STEROID-ACTIVE ALCOHOL DEHYDROGENASE AT 1.54 A RESOLUTION

PDB ID 1ee2

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