1mc5: Difference between revisions
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==Ternary complex of Human glutathione-dependent formaldehyde dehydrogenase with S-(hydroxymethyl)glutathione and NADH== | ==Ternary complex of Human glutathione-dependent formaldehyde dehydrogenase with S-(hydroxymethyl)glutathione and NADH== | ||
<StructureSection load='1mc5' size='340' side='right' caption='[[1mc5]], [[Resolution|resolution]] 2.60Å' scene=''> | <StructureSection load='1mc5' size='340' side='right'caption='[[1mc5]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1mc5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MC5 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[1mc5]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MC5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1MC5 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AHE:2-AMINO-4-[1-CARBOXYMETHYL-CARBAMOYL)-2-HYDROXYMETHYLSULFANYL-ETHYLCARBAMOYL]-BUTYRIC+ACID'>AHE</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AHE:2-AMINO-4-[1-CARBOXYMETHYL-CARBAMOYL)-2-HYDROXYMETHYLSULFANYL-ETHYLCARBAMOYL]-BUTYRIC+ACID'>AHE</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADH5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ADH5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1mc5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1mc5 OCA], [http://pdbe.org/1mc5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1mc5 RCSB], [http://www.ebi.ac.uk/pdbsum/1mc5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1mc5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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==See Also== | ==See Also== | ||
*[[Alcohol dehydrogenase|Alcohol dehydrogenase]] | *[[Alcohol dehydrogenase 3D structures|Alcohol dehydrogenase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Bosron, W F]] | [[Category: Bosron, W F]] | ||
[[Category: Hurley, T D]] | [[Category: Hurley, T D]] | ||
Revision as of 11:36, 2 December 2020
Ternary complex of Human glutathione-dependent formaldehyde dehydrogenase with S-(hydroxymethyl)glutathione and NADHTernary complex of Human glutathione-dependent formaldehyde dehydrogenase with S-(hydroxymethyl)glutathione and NADH
Structural highlights
Function[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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman glutathione-dependent formaldehyde dehydrogenase plays an important role in the metabolism of glutathione adducts such as S-(hydroxymethyl)glutathione and S-nitrosoglutathione. The role of specific active site residues in binding these physiologically important substrates and the structural changes during the catalytic cycle of glutathione-dependent formaldehyde dehydrogenase was examined by determining the crystal structure of a ternary complex with S-(hydroxymethyl)glutathione and the reduced coenzyme to 2.6 A resolution. The formation of the ternary complex caused the movement of the catalytic domain toward the coenzyme-binding domain. This represents the first observation of domain closure in glutathione-dependent formaldehyde dehydrogenase in response to substrate binding. A water molecule adjacent to the 2'-ribose hydroxyl of NADH suggests that the alcohol proton is relayed to solvent directly from the coenzyme, rather than through the action of the terminal histidine residue as observed in the proton relay system for class I alcohol dehydrogenases. S-(Hydroxymethyl)glutathione is directly coordinated to the active site zinc and forms interactions with the highly conserved residues Arg114, Asp55, Glu57, and Thr46. The active site zinc has a tetrahedral coordination environment with Cys44, His66, and Cys173 as the three protein ligands in addition to S-(hydroxymethyl)glutathione. This is in contrast to zinc coordination in the binary coenzyme complex where all of the ligands were contributed by the enzyme and included Glu67 as the fourth protein ligand. This change in zinc coordination is accomplished by an approximately 2.3 A movement of the catalytic zinc. Human glutathione-dependent formaldehyde dehydrogenase. Structural changes associated with ternary complex formation.,Sanghani PC, Bosron WF, Hurley TD Biochemistry. 2002 Dec 24;41(51):15189-94. PMID:12484756[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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