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| | <StructureSection load='6vwf' size='340' side='right'caption='[[6vwf]], [[Resolution|resolution]] 2.64Å' scene=''> | | <StructureSection load='6vwf' size='340' side='right'caption='[[6vwf]], [[Resolution|resolution]] 2.64Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vwf]] 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=6VWF OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VWF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vwf]] 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=6VWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VWF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 2.64Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ALDH9A1, ALDH4, ALDH7, ALDH9 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vwf OCA], [http://pdbe.org/6vwf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vwf RCSB], [http://www.ebi.ac.uk/pdbsum/6vwf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vwf 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=6vwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vwf OCA], [https://pdbe.org/6vwf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vwf RCSB], [https://www.ebi.ac.uk/pdbsum/6vwf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vwf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AL9A1_HUMAN AL9A1_HUMAN]] Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine. Catalyzes the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction.<ref>PMID:10702312</ref> | + | [https://www.uniprot.org/uniprot/AL9A1_HUMAN AL9A1_HUMAN] Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine. Catalyzes the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction.<ref>PMID:10702312</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 6vwf" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6vwf" 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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Tanner, J J]] | + | [[Category: Tanner JJ]] |
| - | [[Category: Wyatt, J W]] | + | [[Category: Wyatt JW]] |
| - | [[Category: Aldehyde dehydrogenase]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
AL9A1_HUMAN Converts gamma-trimethylaminobutyraldehyde into gamma-butyrobetaine. Catalyzes the irreversible oxidation of a broad range of aldehydes to the corresponding acids in an NAD-dependent reaction.[1]
Publication Abstract from PubMed
Aldehyde dehydrogenase 9A1 (ALDH9A1) is a human enzyme that catalyzes the NAD(+)-dependent oxidation of the carnitine precursor 4-trimethylaminobutyraldehyde to 4-N-trimethylaminobutyrate. Here we show that the broad-spectrum ALDH inhibitor diethylaminobenzaldehyde (DEAB) reversibly inhibits ALDH9A1 in a time-dependent manner. Possible mechanisms of inhibition include covalent reversible inactivation involving the thiohemiacetal intermediate and slow, tight-binding inhibition. Two crystal structures of ALDH9A1 are reported, including the first of the enzyme complexed with NAD(+). One of the structures reveals the active conformation of the enzyme, in which the Rossmann dinucleotide-binding domain is fully ordered and the inter-domain linker adopts the canonical beta-hairpin observed in other ALDH structures. The oligomeric structure of ALDH9A1 was investigated using analytical ultracentrifugation, small-angle X-ray scattering, and negative stain electron microscopy. These data show that ALDH9A1 forms the classic ALDH superfamily dimer-of-dimers tetramer in solution. Our results suggest that the presence of an aldehyde substrate and NAD(+) promotes isomerization of the enzyme into the active conformation.
Inhibition, crystal structures, and in-solution oligomeric structure of aldehyde dehydrogenase 9A1.,Wyatt JW, Korasick DA, Qureshi IA, Campbell AC, Gates KS, Tanner JJ Arch Biochem Biophys. 2020 Jul 24:108477. doi: 10.1016/j.abb.2020.108477. PMID:32717224[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Vaz FM, Fouchier SW, Ofman R, Sommer M, Wanders RJ. Molecular and biochemical characterization of rat gamma-trimethylaminobutyraldehyde dehydrogenase and evidence for the involvement of human aldehyde dehydrogenase 9 in carnitine biosynthesis. J Biol Chem. 2000 Mar 10;275(10):7390-4. PMID:10702312
- ↑ Wyatt JW, Korasick DA, Qureshi IA, Campbell AC, Gates KS, Tanner JJ. Inhibition, crystal structures, and in-solution oligomeric structure of aldehyde dehydrogenase 9A1. Arch Biochem Biophys. 2020 Jul 24:108477. doi: 10.1016/j.abb.2020.108477. PMID:32717224 doi:http://dx.doi.org/10.1016/j.abb.2020.108477
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