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| | ==Structure of aminoadipate-semialdehyde dehydrogenase== | | ==Structure of aminoadipate-semialdehyde dehydrogenase== |
| - | <StructureSection load='2j6l' size='340' side='right' caption='[[2j6l]], [[Resolution|resolution]] 1.30Å' scene=''> | + | <StructureSection load='2j6l' size='340' side='right'caption='[[2j6l]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2j6l]] is a 8 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=2J6L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2J6L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2j6l]] is a 8 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=2J6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J6L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.3Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Aldehyde_dehydrogenase_(NAD(+)) Aldehyde dehydrogenase (NAD(+))], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.2.1.3 1.2.1.3] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BR:BROMIDE+ION'>BR</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAI:1,4-DIHYDRONICOTINAMIDE+ADENINE+DINUCLEOTIDE'>NAI</scene></td></tr> |
| - | <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=2j6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j6l OCA], [http://pdbe.org/2j6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2j6l RCSB], [http://www.ebi.ac.uk/pdbsum/2j6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2j6l ProSAT]</span></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=2j6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j6l OCA], [https://pdbe.org/2j6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j6l RCSB], [https://www.ebi.ac.uk/pdbsum/2j6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j6l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Disease == |
| | + | [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 == |
| | + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Aldehyde dehydrogenase|Aldehyde dehydrogenase]] | + | *[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arrowsmith, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Bunkoczi, G]] | + | [[Category: Arrowsmith C]] |
| - | [[Category: Debreczeni, J E]] | + | [[Category: Bunkoczi G]] |
| - | [[Category: Delft, F von]] | + | [[Category: Debreczeni JE]] |
| - | [[Category: Edwards, A]] | + | [[Category: Edwards A]] |
| - | [[Category: Guo, K]] | + | [[Category: Guo K]] |
| - | [[Category: Oppermann, U]] | + | [[Category: Oppermann U]] |
| - | [[Category: Smee, C]] | + | [[Category: Smee C]] |
| - | [[Category: Sundstrom, M]] | + | [[Category: Sundstrom M]] |
| - | [[Category: Weigelt, J]] | + | [[Category: Weigelt J]] |
| - | [[Category: Aldehyde dehydrogenase]] | + | [[Category: Von Delft F]] |
| - | [[Category: Lysine catabolism]]
| + | |
| - | [[Category: Nad]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Reductase]]
| + | |
| 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]
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 PubMed
Mammalian ALDH7A1 is homologous to plant ALDH7B1, an enzyme that protects against various forms of stress, such as salinity, dehydration, and osmotic stress. It is known that mutations in the human ALDH7A1 gene cause pyridoxine-dependent and folic acid-responsive seizures. Herein, we show for the first time that human ALDH7A1 protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes. Human ALDH7A1 expression in Chinese hamster ovary cells attenuated osmotic stress-induced apoptosis caused by increased extracellular concentrations of sucrose or sodium chloride. Purified recombinant ALDH7A1 efficiently metabolized a number of aldehyde substrates, including the osmolyte precursor, betaine aldehyde, lipid peroxidation-derived aldehydes, and the intermediate lysine degradation product, alpha-aminoadipic semialdehyde. The crystal structure for ALDH7A1 supports the enzyme's substrate specificities. Tissue distribution studies in mice showed the highest expression of ALDH7A1 protein in liver, kidney, and brain, followed by pancreas and testes. ALDH7A1 protein was found in the cytosol, nucleus, and mitochondria, making it unique among the aldehyde dehydrogenase enzymes. Analysis of human and mouse cDNA sequences revealed mitochondrial and cytosolic transcripts that are differentially expressed in a tissue-specific manner in mice. In conclusion, ALDH7A1 is a novel aldehyde dehydrogenase expressed in multiple subcellular compartments that protects against hyperosmotic stress by generating osmolytes and metabolizing toxic aldehydes.
Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress.,Brocker C, Lassen N, Estey T, Pappa A, Cantore M, Orlova VV, Chavakis T, Kavanagh KL, Oppermann U, Vasiliou V J Biol Chem. 2010 Jun 11;285(24):18452-63. Epub 2010 Mar 5. PMID:20207735[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
- ↑ 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
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