Literature summary for 1.2.1.3 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 .

Search for more literature for 1.2.1.3

Cloned(Commentary)

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

Protein Variants

Protein Variants	Comment	Organism
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
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
additional information	construction of a C-terminal truncation mutant DELTA504-511 lacking the last eight residues	Homo sapiens
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]

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

Molecular Weight [Da]

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

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
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)

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

Subunits

Subunits	Comment	Organism
More	sedimentation equilibrium analysis, and analytical ultracentifugation, dimer?tetramer self-association model	Homo sapiens
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

Synonyms	Comment	Organism
aldehyde dehydrogenase 7A1	-	Homo sapiens
Aldh7a1	-	Homo sapiens

Temperature Optimum [°C]

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

Turnover Number [1/s]

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

pH Optimum

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

Cofactor

Cofactor	Comment	Organism	Structure
NAD+	-	Homo sapiens

General Information

General Information	Comment	Organism
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
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
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]

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

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Release 2023.1 (January 2023)