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Literature summary extracted from

  • Korasick, D.A.; Wyatt, J.W.; Luo, M.; Laciak, A.R.; Ruddraraju, K.; Gates, K.S.; Henzl, M.T.; Tanner, J.J.
    Importance of the C-terminus of aldehyde dehydrogenase 7A1 for oligomerization and catalytic activity (2017), Biochemistry, 56, 5910-5919 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.2.1.3 recombinant expression of wild-type and mutant enzymes in Escherichia coli Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
1.2.1.3 A505P site-directed mutagenesis, the mutant enzyme exhibits a profound kinetic defect characterized by markedly elevated Michaelis constants for alpha-aminoadipate semialdehyde, suggesting that the mutated residue is important for substrate binding. The mutant enzyme is defective in tetramer formation, and shows highly reduced activity compared to wild-type Homo sapiens
1.2.1.3 A505P/Q506K site-directed mutagenesis, the mutant enzyme exhibits a profound kinetic defect characterized by markedly elevated Michaelis constants for alpha-aminoadipate semialdehyde, suggesting that the mutated residues are important for substrate binding. The mutant enzyme is defective in tetramer formation, and shows highly reduced activity compared to wild-type. Structure analysis of the protomer of ALDH7A1 with the mutated residues Ala505 and Gln506, PDB ID 4ZUL Homo sapiens
1.2.1.3 additional information construction of a C-terminal truncation mutant DELTA504-511 lacking the last eight residues Homo sapiens
1.2.1.3 Q506K site-directed mutagenesis, the mutant enzyme exhibits a profound kinetic defect characterized by markedly elevated Michaelis constants for alpha-aminoadipate semialdehyde, suggesting that the mutated residue is important for substrate binding. The mutant enzyme is defective in tetramer formation, and shows highly reduced activity compared to wild-type Homo sapiens

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
1.2.1.3 additional information
-
 additional information Michaelis-Menten steady-state kinetics of wild-type and mutant enzymes Homo sapiens
1.2.1.3 0.064
-
 alpha-aminoadipate semialdehyde pH 8.0, 26°C, recombinant wild-type enzyme Homo sapiens
1.2.1.3 0.63
-
 alpha-aminoadipate semialdehyde pH 8.0, 26°C, recombinant mutant A505P Homo sapiens

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
1.2.1.3 157600
-
 sedimentation equilibrium analysis, and analytical ultracentifugation Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.2.1.3 alpha-aminoadipate semialdehyde + NAD+ + H2O Homo sapiens
-
 alpha-aminoadipate + NADH + H+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.2.1.3 Homo sapiens
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.2.1.3 recombinant wild-type and mutant enzymes from Escherichia coli by nickel affinity chromatography, tag cleavage by TEV protease, dialysis, and gel filtration Homo sapiens

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.2.1.3 alpha-aminoadipate semialdehyde + NAD+ + H2O
-
 Homo sapiens alpha-aminoadipate + NADH + H+
-
 ?

Subunits

EC Number Subunits Comment Organism
1.2.1.3 More sedimentation equilibrium analysis, and analytical ultracentifugation, dimer?tetramer self-association model Homo sapiens
1.2.1.3 tetramer a Dimer-of-dimers tetramer, analysis of the quaternary structural interactions that stabilize the aldehyde-binding site in the closed state, overview Homo sapiens

Synonyms

EC Number Synonyms Comment Organism
1.2.1.3 aldehyde dehydrogenase 7A1
-
 Homo sapiens
1.2.1.3 Aldh7a1
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.2.1.3 26
-
 assay at Homo sapiens

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.2.1.3 0.3
-
 alpha-aminoadipate semialdehyde pH 8.0, 26°C, recombinant wild-type enzyme Homo sapiens
1.2.1.3 1
-
 alpha-aminoadipate semialdehyde pH 8.0, 26°C, recombinant mutant A505P Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.2.1.3 8
-
 assay at Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.2.1.3 NAD+
-
 Homo sapiens

General Information

EC Number General Information Comment Organism
1.2.1.3 malfunction enzyme residues Ala505 and Gln506 interact with the conserved aldehyde anchor loop structure in the closed state. The apparent involvement of these residues in catalysis is significant because they are replaced by Pro505 and Lys506 in a genetic deletion (c.1512delG) that causes pyridoxine-dependent epilepsy, a rare autosomal recessive disorder that typically presents with seizures in the first days of life. Compromised ALDH7A1 activity leads to increased levels of alpha-aminoadipate semialdehyde and DELTA1-piperideine-6-carboxylic acid (P6C), the cyclized form of alpha-aminoadipate semialdehyde. P6C reacts with a ubiquitous cofactor, pyridoxal 5'-phosphate, and the resulting adduct is incapable as an enzyme cofactor. Site-directed single mutations A505P and Q506K and double mutation A505P/Q506K as well as the C-terminal truncation mutant DELTA504-511, which lacks residues 504-511, are analyzed with steady-state kinetics assays and analytical ultracentrifugation. The mutant enzymes exhibit a common phenotype characterized by a very high Km for alpha-aminoadipate semialdehyde (AASAL) and a perturbed self-association equilibrium Homo sapiens
1.2.1.3 additional information residues Ala505 and Gln506, that interact with the conserved aldehyde anchor loop structure in the closed state, are involved in catalysis. Discovery of the C-terminus as a mobile part of the active site. The C-terminus of ALDH7A1 is crucial for the maintenance of both the oligomeric state and the catalytic activity Homo sapiens
1.2.1.3 physiological function aldehyde dehydrogenase 7A1 (ALDH7A1) catalyzes the terminal step of lysine catabolism, the NAD+-dependent oxidation of alpha-aminoadipate semialdehyde to alpha-aminoadipate Homo sapiens

kcat/KM [mM/s]

EC Number kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
1.2.1.3 1.6
-
 alpha-aminoadipate semialdehyde pH 8.0, 26°C, recombinant mutant A505P Homo sapiens
1.2.1.3 4.7
-
 alpha-aminoadipate semialdehyde pH 8.0, 26°C, recombinant wild-type enzyme Homo sapiens