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| - | [[Image:1mgo.gif|left|200px]] | |
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| - | {{Structure
| + | ==Horse Liver Alcohol Dehydrogenase Phe93Ala Mutant== |
| - | |PDB= 1mgo |SIZE=350|CAPTION= <scene name='initialview01'>1mgo</scene>, resolution 1.20Å
| + | <StructureSection load='1mgo' size='340' side='right'caption='[[1mgo]], [[Resolution|resolution]] 1.20Å' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND= <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PFB:2,3,4,5,6-PENTAFLUOROBENZYL+ALCOHOL'>PFB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | + | <table><tr><td colspan='2'>[[1mgo]] 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=1MGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1MGO FirstGlance]. <br> |
| - | |ACTIVITY= <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.2Å</td></tr> |
| - | |GENE= M64864 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9796 Equus caballus])
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PFB:2,3,4,5,6-PENTAFLUOROBENZYL+ALCOHOL'>PFB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | |DOMAIN=
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1mgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mgo OCA], [https://pdbe.org/1mgo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1mgo RCSB], [https://www.ebi.ac.uk/pdbsum/1mgo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1mgo ProSAT]</span></td></tr> |
| - | |RELATEDENTRY=[[1hld|1HLD]], [[1mg0|1MG0]]
| + | </table> |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1mgo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mgo OCA], [http://www.ebi.ac.uk/pdbsum/1mgo PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1mgo RCSB]</span>
| + | == Function == |
| - | }}
| + | [https://www.uniprot.org/uniprot/ADH1E_HORSE ADH1E_HORSE] |
| | + | == 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/mg/1mgo_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=1mgo ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''Horse Liver Alcohol Dehydrogenase Phe93Ala Mutant'''
| + | ==See Also== |
| - | | + | *[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]] |
| - | | + | __TOC__ |
| - | ==Overview== | + | </StructureSection> |
| - | The relationship between substrate mobility and catalysis was studied with wild-type and Phe93Ala (F93A) horse liver alcohol dehydrogenase (ADH). Wild-type ADH binds 2,3,4,5,6-pentafluorobenzyl alcohol in one position as shown by X-ray results, and (19)F NMR shows five resonances for the fluorines of the bound alcohol. The two meta-fluorines exchange positions with a rate constant of about 4 s(-1), indicating that mobility (ring flipping) of the benzyl alcohol is relatively restricted. The wild-type enzyme binds 2,3-difluorobenzyl alcohol in two alternative conformations that are related by a ring flip and a small translation of the fluorinated benzene ring, and the (19)F NMR spectrum shows three resonances for the two bound fluorines, consistent with the two orientations. Phe-93 interacts with the bound benzyl alcohols, and the F93A substitution decreases the rate constants for hydride transfer for benzyl alcohol oxidation and benzaldehyde reduction by 7.4- and 130-fold, respectively. The structure of F93A ADH crystallized with NAD(+) and 2,3,4,5,6-pentafluorobenzyl alcohol is similar to the structure of the wild-type enzyme complex except that the pentafluorobenzyl alcohol is not found in one position. The (19)F NMR spectrum of the F93A ADH-NAD(+)-pentafluorobenzyl alcohol complex shows three resonances for the bound fluorines. Line shape analysis of the spectrum suggests the bound pentafluorobenzyl ring undergoes rapid ring-flipping at about 20 000 s(-1). The F93A substitution greatly increases the mobility of the benzyl alcohol but modestly and differentially decreases the probability that the substrate is preorganized for hydride transfer.
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| - | | + | |
| - | ==About this Structure==
| + | |
| - | 1MGO is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Equus_caballus Equus caballus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MGO OCA].
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| - | | + | |
| - | ==Reference==
| + | |
| - | Mobility of fluorobenzyl alcohols bound to liver alcohol dehydrogenases as determined by NMR and X-ray crystallographic studies., Rubach JK, Plapp BV, Biochemistry. 2002 Dec 31;41(52):15770-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12501206 12501206]
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| - | [[Category: Alcohol dehydrogenase]]
| + | |
| | [[Category: Equus caballus]] | | [[Category: Equus caballus]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Plapp, B V.]] | + | [[Category: Plapp BV]] |
| - | [[Category: Rubach, J K.]] | + | [[Category: Rubach JK]] |
| - | [[Category: alcohol]]
| + | |
| - | [[Category: dehydrogenase]]
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| - | [[Category: mutant]]
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| - | [[Category: nicotinamide coenzyme]]
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| - | [[Category: substrate binding site]]
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| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:15:48 2008''
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