6qap: Difference between revisions
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<StructureSection load='6qap' size='340' side='right'caption='[[6qap]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='6qap' size='340' side='right'caption='[[6qap]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6qap]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6qap]] 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=6QAP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QAP 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]] 2.3Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=6qap FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qap OCA], [https://pdbe.org/6qap PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qap RCSB], [https://www.ebi.ac.uk/pdbsum/6qap PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qap ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</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 6qap" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6qap" 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: Morera | [[Category: Morera S]] | ||
[[Category: Vigouroux | [[Category: Vigouroux A]] | ||
Latest revision as of 14:56, 24 January 2024
Structure of the human aldehyde dehydrogenase 9A1 in C2 space groupStructure of the human aldehyde dehydrogenase 9A1 in C2 space group
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 dehydrogenases (ALDHs) constitute a superfamily of NAD(P)(+)-dependent enzymes, which detoxify aldehydes produced in various metabolic pathways to the corresponding carboxylic acids. Among the 19 human ALDHs, the cytosolic ALDH9A1 has so far never been fully enzymatically characterized and its structure is still unknown. Here, we report complete molecular and kinetic properties of human ALDH9A1 as well as three crystal forms at 2.3 A, 2.9 A and 2.5 A resolution. We show that ALDH9A1 exhibits wide substrate specificity to aminoaldehydes, aliphatic and aromatic aldehydes with a clear preference for gamma -trimethylaminobutyraldehyde (TMABAL). The structure of ALDH9A1 reveals that the enzyme assembles as a tetramer. Each ALDH monomer displays a typical ALDHs fold composed of an oligomerization domain, a coenzyme domain, a catalytic domain and an inter-domain linker highly conserved in amino-acid sequence and folding. Nonetheless, structural comparison reveals a position and a fold of the inter-domain linker of ALDH9A1 never observed in any other ALDH so far. This unique difference is not compatible with the presence of a bound substrate and a large conformational rearrangement of the linker up to 30 A has to occur to allow the access of the substrate channel. Moreover, the alphabetaE region consisting of an alpha-helix and a beta-strand of the coenzyme domain at the dimer interface are disordered, likely due to the loss of interactions with the inter-domain linker, which leads to incomplete NAD(+) binding pocket. Kinetic and structural analysis of human ALDH9A1.,Koncitikova R, Vigouroux A, Kopecna M, Sebela M, Morera S, Kopecny D Biosci Rep. 2019 Mar 26. pii: BSR20190558. doi: 10.1042/BSR20190558. PMID:30914451[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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