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| | ==Structure ALDH7A1 inactivated by 4-diethylaminobenzaldehyde== | | ==Structure ALDH7A1 inactivated by 4-diethylaminobenzaldehyde== |
| - | <StructureSection load='4x0u' size='340' side='right' caption='[[4x0u]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='4x0u' size='340' side='right'caption='[[4x0u]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4x0u]] is a 4 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=4X0U OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4X0U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4x0u]] is a 4 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=4X0U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X0U FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3W9:4-(DIETHYLAMINO)BENZALDEHYDE'>3W9</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3W9:4-(DIETHYLAMINO)BENZALDEHYDE'>3W9</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4x0t|4x0t]]</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=4x0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x0u OCA], [https://pdbe.org/4x0u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x0u RCSB], [https://www.ebi.ac.uk/pdbsum/4x0u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x0u ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALDH7A1, ATQ1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4x0u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x0u OCA], [http://pdbe.org/4x0u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4x0u RCSB], [http://www.ebi.ac.uk/pdbsum/4x0u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4x0u ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/AL7A1_HUMAN AL7A1_HUMAN]] Pyridoxine-dependent epilepsy. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/AL7A1_HUMAN AL7A1_HUMAN] Pyridoxine-dependent epilepsy. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AL7A1_HUMAN AL7A1_HUMAN]] Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism.<ref>PMID:16491085</ref> <ref>PMID:20207735</ref> | + | [https://www.uniprot.org/uniprot/AL7A1_HUMAN AL7A1_HUMAN] Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism.<ref>PMID:16491085</ref> <ref>PMID:20207735</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4x0u" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4x0u" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Luo, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Tanner, J J]] | + | [[Category: Luo M]] |
| - | [[Category: Aldehyde dehydrogenase]] | + | [[Category: Tanner JJ]] |
| - | [[Category: Lysine catabolism]]
| + | |
| - | [[Category: Nad]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
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| Structural highlights
Disease
AL7A1_HUMAN Pyridoxine-dependent epilepsy. The disease is caused by mutations affecting the gene represented in this entry.
Function
AL7A1_HUMAN Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism.[1] [2]
Publication Abstract from PubMed
There is growing interest in aldehyde dehydrogenases (ALDHs) because of their overexpression in cancer stem cells and the ability to mediate resistance to cancer drugs. Here, we report the first crystal structure of an aldehyde dehydrogenase complexed with the inhibitor 4-diethylaminobenzaldehyde (DEAB). Contrary to the widely held belief that DEAB is a reversible inhibitor of ALDHs, we show that DEAB irreversibly inactivates ALDH7A1 via formation of a stable, covalent acyl-enzyme species.
Diethylaminobenzaldehyde Is a Covalent, Irreversible Inactivator of ALDH7A1.,Luo M, Gates KS, Henzl MT, Tanner JJ ACS Chem Biol. 2015 Jan 6. PMID:25554827[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA, Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT. Mutations in antiquitin in individuals with pyridoxine-dependent seizures. Nat Med. 2006 Mar;12(3):307-9. Epub 2006 Feb 19. PMID:16491085 doi:http://dx.doi.org/nm1366
- ↑ Brocker C, Lassen N, Estey T, Pappa A, Cantore M, Orlova VV, Chavakis T, Kavanagh KL, Oppermann U, Vasiliou V. Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress. J Biol Chem. 2010 Jun 11;285(24):18452-63. Epub 2010 Mar 5. PMID:20207735 doi:10.1074/jbc.M109.077925
- ↑ Luo M, Gates KS, Henzl MT, Tanner JJ. Diethylaminobenzaldehyde Is a Covalent, Irreversible Inactivator of ALDH7A1. ACS Chem Biol. 2015 Jan 6. PMID:25554827 doi:http://dx.doi.org/10.1021/cb500977q
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