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== | ==Structural evidence for a ligand coordination switch in liver alcohol dehydrogenase== | ||
<StructureSection load='2jhg' size='340' side='right'caption='[[2jhg]], [[Resolution|resolution]] 1.20Å' scene=''> | |||
[[ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2jhg]] 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=2JHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JHG 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]] 1.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IBO:2-METHYLPROPANAMIDE'>IBO</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2jhg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jhg OCA], [https://pdbe.org/2jhg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jhg RCSB], [https://www.ebi.ac.uk/pdbsum/2jhg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jhg ProSAT]</span></td></tr> | |||
</table> | |||
== 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/jh/2jhg_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=2jhg ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The use of substrate analogues as inhibitors provides a way to understand and manipulate enzyme function. Here we report two 1 A resolution crystal structures of liver alcohol dehydrogenase in complex with NADH and two inhibitors: dimethyl sulfoxide and isobutyramide. Both structures present a dynamic state of inhibition. In the dimethyl sulfoxide complex structure, the inhibitor is caught in transition on its way to the active site using a flash-freezing protocol and a cadmium-substituted enzyme. One inhibitor molecule is partly located in the first and partly in the second coordination sphere of the active site metal. A hydroxide ion bound to the active site metal lies close to the pyridine ring of NADH, which is puckered in a twisted boat conformation. The cadmium ion is coordinated by both the hydroxide ion and the inhibitor molecule, providing structural evidence of a coordination switch at the active site metal ion. The structure of the isobutyramide complex reveals the partial formation of an adduct between the isobutyramide inhibitor and NADH. It provides evidence of the contribution of a shift from the keto to the enol tautomer during aldehyde reduction. The different positions of the inhibitors further refine the knowledge of the dynamics of the enzyme mechanism and explain how the crowded active site can facilitate the presence of a substrate and a metal-bound hydroxide ion. | |||
Structural evidence for a ligand coordination switch in liver alcohol dehydrogenase.,Meijers R, Adolph HW, Dauter Z, Wilson KS, Lamzin VS, Cedergren-Zeppezauer ES Biochemistry. 2007 May 8;46(18):5446-54. Epub 2007 Apr 13. PMID:17429946<ref>PMID:17429946</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2jhg" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Equus caballus]] | [[Category: Equus caballus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Adolph | [[Category: Adolph HW]] | ||
[[Category: Cedergren-Zeppezauer | [[Category: Cedergren-Zeppezauer ES]] | ||
[[Category: Dauter | [[Category: Dauter Z]] | ||
[[Category: Lamzin | [[Category: Lamzin VS]] | ||
[[Category: Meijers | [[Category: Meijers R]] | ||
[[Category: Wilson | [[Category: Wilson KS]] | ||
Latest revision as of 17:48, 13 December 2023
Structural evidence for a ligand coordination switch in liver alcohol dehydrogenaseStructural evidence for a ligand coordination switch in liver alcohol dehydrogenase
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe use of substrate analogues as inhibitors provides a way to understand and manipulate enzyme function. Here we report two 1 A resolution crystal structures of liver alcohol dehydrogenase in complex with NADH and two inhibitors: dimethyl sulfoxide and isobutyramide. Both structures present a dynamic state of inhibition. In the dimethyl sulfoxide complex structure, the inhibitor is caught in transition on its way to the active site using a flash-freezing protocol and a cadmium-substituted enzyme. One inhibitor molecule is partly located in the first and partly in the second coordination sphere of the active site metal. A hydroxide ion bound to the active site metal lies close to the pyridine ring of NADH, which is puckered in a twisted boat conformation. The cadmium ion is coordinated by both the hydroxide ion and the inhibitor molecule, providing structural evidence of a coordination switch at the active site metal ion. The structure of the isobutyramide complex reveals the partial formation of an adduct between the isobutyramide inhibitor and NADH. It provides evidence of the contribution of a shift from the keto to the enol tautomer during aldehyde reduction. The different positions of the inhibitors further refine the knowledge of the dynamics of the enzyme mechanism and explain how the crowded active site can facilitate the presence of a substrate and a metal-bound hydroxide ion. Structural evidence for a ligand coordination switch in liver alcohol dehydrogenase.,Meijers R, Adolph HW, Dauter Z, Wilson KS, Lamzin VS, Cedergren-Zeppezauer ES Biochemistry. 2007 May 8;46(18):5446-54. Epub 2007 Apr 13. PMID:17429946[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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