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Literature summary extracted from

  • Wyatt, J.W.; Korasick, D.A.; Qureshi, I.A.; Campbell, A.C.; Gates, K.S.; Tanner, J.J.
    Inhibition, crystal structures, and in-solution oligomeric structure of aldehyde dehydrogenase 9A1 (2020), Arch. Biochem. Biophys., 691, 108477 .
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.2.1.47 additional information the presence of an aldehyde substrate and NAD+ promotes isomerization of the enzyme into the active conformation Homo sapiens

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.2.1.47 recombinant expression of SUMO-His6-tagged ALDH9A1 in Escherichia coli strain BL21(DE3) Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.2.1.47 purified recombinant detagged enzyme in complex with NAD+ and inhibitor diethylaminobenzaldehyde, hanging drop vapour diffusion method, mixing of 6 mg/ml protein in 50 mM Tris-HCl, pH 8.0, 600 mM NaCl, 5% glycerol, 0.5 mM TCE, 5 mM DEAB, and 10 mM NAD+, with reservoir solution containing 0.1 M NaCl, 0.05 M Bis-Tris, pH 6.5, 0.1 M ammonium acetate, 0.05 M HEPES, pH 7.5, and 25% w/v PEG 3350, method optimization, X-ray diffraction structure determination and analysis at 2.50-2.64 A resolution, molecular replacement using structures of cod liver betaine ALDH (PDB ID 1A4S) and apo-ALDH9A1 (PDB ID 6QAP) as search models, modeling Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.2.1.47 diethylaminobenzaldehyde DEAB, the broad-spectrum ALDH inhibitor reversibly inhibits ALDH9A1 in a time-dependent manner by a covalent reversible mechanism of inhibition, mechanism analysis, overview Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.2.1.47 additional information
-
 additional information steady-state Michaelis-Menten kinetics Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
1.2.1.47 cytosol
-
 Homo sapiens 5829
-

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.2.1.47 223000
-
 recombinant detagged enzyme, gel filtration Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.2.1.47 3,4-dihydroxyphenylacetaldehyde + NAD+ + H2O Homo sapiens a dopamine metabolite 3,4-dihydroxyphenylacetate + NADH + H+
-
 ?
1.2.1.47 4-trimethylaminobutyraldehyde + NAD+ + H2O Homo sapiens a carnitine precursor 4-N-trimethylaminobutyrate + NADH + H+
-
 ?
1.2.1.47 aminobutyraldehyde + NAD+ + H2O Homo sapiens a GABA precursor aminobutyrate + NADH + H+
-
 ?
1.2.1.47 betaine aldehyde + NAD+ + H2O Homo sapiens
-
 betaine + NADH + H+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.2.1.47 Homo sapiens P49189
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.2.1.47 recombinant SUMO-His6-tagged ALDH9A1 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography, cleavage of the SUMO-His tag, dialysis, ultrafiltration, and gel filtration Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.2.1.47 3,4-dihydroxyphenylacetaldehyde + NAD+ + H2O
-
 Homo sapiens 3,4-dihydroxyphenylacetate + NADH + H+
-
 ?
1.2.1.47 3,4-dihydroxyphenylacetaldehyde + NAD+ + H2O a dopamine metabolite Homo sapiens 3,4-dihydroxyphenylacetate + NADH + H+
-
 ?
1.2.1.47 4-trimethylaminobutyraldehyde + NAD+ + H2O strongly preferred substrate Homo sapiens 4-N-trimethylaminobutyrate + NADH + H+
-
 ?
1.2.1.47 4-trimethylaminobutyraldehyde + NAD+ + H2O a carnitine precursor Homo sapiens 4-N-trimethylaminobutyrate + NADH + H+
-
 ?
1.2.1.47 aminobutyraldehyde + NAD+ + H2O
-
 Homo sapiens aminobutyrate + NADH + H+
-
 ?
1.2.1.47 aminobutyraldehyde + NAD+ + H2O a GABA precursor Homo sapiens aminobutyrate + NADH + H+
-
 ?
1.2.1.47 betaine aldehyde + NAD+ + H2O
-
 Homo sapiens betaine + NADH + H+
-
 ?
1.2.1.47 hexanal + NAD+ + H2O
-
 Homo sapiens hexanoate + NADH + H+
-
 ?
1.2.1.47 additional information diethylaminobenzaldehyde (DEAB) is not a substrate for ALDH9A1 Homo sapiens ?
-
-

Subunits

EC Number Subunits Comment Organism
1.2.1.47 More conformation of the inter-domain linker in the P1 ALDH9A1-NAD+ structure, modeling, overview. The in-solution quaternary structure of ALDH9A1 is determined using SAXS Homo sapiens
1.2.1.47 tetramer enzyme ALDH9A1 forms the classic ALDH superfamily dimer-of-dimers tetramer in solution. Analytical ultracentrifugation, small-angle X-ray scattering (SAXS), and negative stain electron microscopy are used for analysis Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.2.1.47 aldehyde dehydrogenase 9A1
-
 Homo sapiens
1.2.1.47 Aldh9a1
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.2.1.47 27
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.2.1.47 8
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.2.1.47 NAD+ enzyme binding structure, enzyme-NAD+ crystal structure analysis, overview. NAD+ binds in the expected site at the C-termini of the beta-strands of the Rossmann fold. NAD+ forms several electrostatic interactions with the protein. The adenine ribose hydrogen bonds with Lys180. The diphosphate interacts with Trp156, Ser233, and Thr236. The nicotinamide ribose of the one complete NAD+ forms a hydrogen bond with Glu391, a residue identically conserved in the ALDH superfamily Homo sapiens

General Information

EC Number General Information Comment Organism
1.2.1.47 evolution aldehyde dehydrogenase 9A1 (ALDH9A1) belongs to the aldehyde dehydrogenase (ALDH) structural superfamily, which is a large group of enzymes that catalyze the NAD+-dependent oxidation of aldehydes to carboxylic acids. The superfamily comprises hundreds of distinct genes, including 19 ALDHs expressed in humans. ALDHs share a common protein fold and catalytic mechanism, but subtle differences in their active sites result in different preferences for the aldehyde substrate. Although ALDH9A1 exhibits the basic ALDH superfamily fold, the structure reveals two remarkable features. First, the final alpha-helix and beta-strand of the Rossmann dinucleotide-binding fold are disordered. Referred to as alphaE-betaE in the closely-related betaine ALDH, these secondary structural elements form extensive interactions with NAD+ in other ALDHs Homo sapiens
1.2.1.47 additional information 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 presence of an aldehyde substrate and NAD+ promotes isomerization of the enzyme into the active conformation Homo sapiens
1.2.1.47 physiological function the major in vivo function of this enzyme is to catalyze the penultimate step of carnitine biosynthesis, the oxidation of TMBAL to 4-N-trimethylaminobutyrate. Carnitine functions in the transport of long-chain fatty acids from the cytosol to the mitochondrial matrix for the synthesis of acyl-CoAs for beta-oxidation. ALDH9A1 functions indirectly in beta-oxidation Homo sapiens