ArticleChemico-biological interactions2017
Impact of disease-Linked mutations targeting the oligomerization interfaces of aldehyde dehydrogenase 7A1.
Article in Chemico-biological interactions, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Targeting ALDH7A1 with covalent inhibitors reveals new chemical space for prostate cancer therapy.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Aminoadipate-semialdehyde synthase, a potential target for substrate reduction therapy in glutaric aciduria type 1.Scientific reports · 2026Article
- Biochemical, structural, and computational analyses of two new clinically identified missense mutations of ALDH7A1.Chemico-biological interactions · 2024Article
- Impact of missense mutations in the ALDH7A1 gene on enzyme structure and catalytic function.Biochimie · 2021Review
- Insights into Aldehyde Dehydrogenase Enzymes: A Structural Perspective.Frontiers in molecular biosciences · 2021Review
- Structural analysis of pathogenic mutations targeting Glu427 of ALDH7A1, the hot spot residue of pyridoxine-dependent epilepsy.Journal of inherited metabolic disease · 2020Article
- Structural and biochemical consequences of pyridoxine-dependent epilepsy mutations that target the aldehyde binding site of aldehyde dehydrogenase ALDH7A1.The FEBS journal · 2020Article
- Structural and Biochemical Characterization of Aldehyde Dehydrogenase 12, the Last Enzyme of Proline Catabolism in Plants.Journal of molecular biology · 2019Article
- NADFEBS letters · 2018Article
- Importance of the C-Terminus of Aldehyde Dehydrogenase 7A1 for Oligomerization and Catalytic Activity.Biochemistry · 2017Article
- Biophysical investigation of type A PutAs reveals a conserved core oligomeric structure.The FEBS journal · 2017Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Aldehyde dehydrogenase 7A1 (ALDH7A1) is involved in lysine catabolism, catalyzing the oxidation of α-aminoadipate semialdehyde to α-aminoadipate. Certain mutations in the ALDH7A1 gene, which are presumed to reduce catalytic activity, cause an autosomal recessive seizure disorder known as pyridoxine-dependent epilepsy (PDE). Although the genetic association between ALDH7A1 and PDE is well established, little is known about the impact of PDE-mutations on the structure and catalytic function of the enzyme. Herein we report the first study of the molecular consequences of PDE mutations using purified ALDH7A1 variants. Eight variants, with mutations in the oligomer interfaces, were expressed in Escherichia coli: P78L, G83E, A129P, G137V, G138V, A149E, G255D, and G263E. All but P78L and G83E were soluble and could be purified. All six soluble mutants were catalytically inactive. The impact of the mutations on oligomerization was assessed by analytical ultracentrifugation. Wild-type ALDH7A1 is shown to exist in a dimer-tetramer equilibrium with a dissociation constant of 16 μM. In contrast to the wild-type enzyme, the variants reside in monomer-dimer equilibria and are apparently incapable of forming a tetrameric species, even at high enzyme concentration. The available evidence suggests that they are misfolded assemblies lacking the three-dimensional structure required for catalysis.
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