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1m6h

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[[Image:1m6h.jpg|left|200px]]<br /><applet load="1m6h" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1m6h, resolution 2.00&Aring;" />
 
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'''Human glutathione-dependent formaldehyde dehydrogenase'''<br />
 
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==Overview==
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==Human glutathione-dependent formaldehyde dehydrogenase==
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The human glutathione-dependent formaldehyde dehydrogenase is unique among the structurally studied members of the alcohol dehydrogenase family in that it follows a random bi bi kinetic mechanism. The structures of an apo form of the enzyme, a binary complex with substrate 12-hydroxydodecanoic acid, and a ternary complex with NAD+ and the inhibitor dodecanoic acid were determined at 2.0, 2.3, and 2.3 A resolution by X-ray crystallography using the anomalous diffraction signal of zinc. The structures of the enzyme and its binary complex with the primary alcohol substrate, 12-hydroxydodecanoic acid, and the previously reported binary complex with the coenzyme show that the binding of the first substrate (alcohol or coenzyme) causes only minor changes to the overall structure of the enzyme. This is consistent with the random mechanism of the enzyme where either of the substrates binds to the free enzyme. The catalytic-domain position in these structures is intermediate to the "closed" and "open" conformations observed in class I alcohol dehydrogenases. More importantly, two different tetrahedral coordination environments of the active site zinc are observed in these structures. In the apoenzyme, the active site zinc is coordinated to Cys44, His66 and Cys173, and a water molecule. In the inhibitor complex, the coordination environment involves Glu67 instead of the solvent water molecule. The coordination environment involving Glu67 as the fourth ligand likely represents an intermediate step during ligand exchange at the active site zinc. These observations provide new insight into metal-assisted catalysis and substrate binding in glutathione-dependent formaldehyde dehydrogenase.
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<StructureSection load='1m6h' size='340' side='right'caption='[[1m6h]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1m6h]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M6H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1M6H 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&#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=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=1m6h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1m6h OCA], [https://pdbe.org/1m6h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1m6h RCSB], [https://www.ebi.ac.uk/pdbsum/1m6h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1m6h ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/ADHX_HUMAN ADHX_HUMAN] Class-III ADH is remarkably ineffective in oxidizing ethanol, but it readily catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione.
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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/m6/1m6h_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=1m6h 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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1M6H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=K:'>K</scene> and <scene name='pdbligand=PO4:'>PO4</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=1M6H 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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Human glutathione-dependent formaldehyde dehydrogenase. Structures of apo, binary, and inhibitory ternary complexes., Sanghani PC, Robinson H, Bosron WF, Hurley TD, Biochemistry. 2002 Sep 3;41(35):10778-86. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12196016 12196016]
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[[Category: Alcohol dehydrogenase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Bosron, W F.]]
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[[Category: Bosron WF]]
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[[Category: Hurley, T D.]]
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[[Category: Hurley TD]]
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[[Category: Robinson, H.]]
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[[Category: Robinson H]]
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[[Category: Sanghani, P C.]]
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[[Category: Sanghani PC]]
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[[Category: K]]
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[[Category: PO4]]
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[[Category: ZN]]
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[[Category: glutathione-dependent formaldehyde dehydrogenase class iii alcohol dehydrogenase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:51:59 2008''
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Current revision

Human glutathione-dependent formaldehyde dehydrogenase

PDB ID 1m6h

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