6vr6: Difference between revisions
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<StructureSection load='6vr6' size='340' side='right'caption='[[6vr6]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='6vr6' size='340' side='right'caption='[[6vr6]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6vr6]] is a 8 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6vr6]] 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=6VR6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VR6 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id=' | <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'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6vr6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vr6 OCA], [https://pdbe.org/6vr6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vr6 RCSB], [https://www.ebi.ac.uk/pdbsum/6vr6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vr6 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [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 6vr6" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6vr6" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Aldehyde dehydrogenase 3D structures|Aldehyde dehydrogenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Tanner | [[Category: Tanner JJ]] | ||
[[Category: Wyatt | [[Category: Wyatt JW]] | ||
Latest revision as of 11:17, 11 October 2023
Structure of ALDH9A1 complexed with NAD+ in space group P1Structure of ALDH9A1 complexed with NAD+ in space group P1
Structural highlights
FunctionAL9A1_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 PubMedAldehyde 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 AlsoReferences
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