ArticleThe EMBO journal2009
Redox-switch modulation of human SSADH by dynamic catalytic loop.
Article in The EMBO journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 102 citations in OpenAlex.
- Succinic semialdehyde dehydrogenase deficiency: exploring the relationship between ALDH5A1 variants and molecular effect on SSADH.Orphanet journal of rare diseases · 2026Article
- Cultivated Fritillaria cirrhosa bulbs shows comparable chemistry and efficacy to wild-type in Chuanbei Pipa Tangjiang: a metabolomics study.Scientific reports · 2026Article
- Biocompatible ligand balancing in transition metal coordination enables benign in-cell protein arylation.Nature chemistry · 2026Article
- Not just a cycle: mitochondrial CsgabD is involved in GABA metabolism during citrus defense against biotic stress.Plant molecular biology · 2026Article
- A novel hereditary encephalopathy in four related Labrador Retrievers associated with a missense variant in the ALDH5A1 gene.Journal of veterinary internal medicine · 2026Article
- Central Dysmyelination in SSADH-Deficient Humans and Mice.Annals of clinical and translational neurology · 2025Observational
- The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders.International journal of molecular sciences · 2025Review
- The aldehyde dehydrogenase superfamilies: correlations and deviations in structure and function.Applied microbiology and biotechnology · 2025Review
- A crucial active site network of titratable residues guides catalysis and NADProtein science : a publication of the Protein Society · 2025Article
- Transcriptomic responses in the nervous system and correlated behavioural changes of a cephalopod exposed to ocean acidification.BMC genomics · 2024Article
- Clinical features and ALDH5A1 gene findings in 13 Chinese cases with succinic semialdehyde dehydrogenase deficiency.BMC medical genomics · 2024Article
- Discovery of a Tunable Heterocyclic Electrophile 4-Chloro-pyrazolopyridine That Defines a Unique Subset of Ligandable Cysteines.ACS chemical biology · 2024Article
- Functional Characterization of a Spectrum of Genetic Variants in a Family with Succinic Semialdehyde Dehydrogenase Deficiency.International journal of molecular sciences · 2024Article
- Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder.Journal of neurodevelopmental disorders · 2024Article
- Biochemical and structural elucidation of the L-carnitine degradation pathway of the human pathogenFrontiers in microbiology · 2024Article
- Phenotypic correlates of structural and functional protein impairments resultant from ALDH5A1 variants.Human genetics · 2023Article
- Molecular basis of sulfolactate synthesis by sulfolactaldehyde dehydrogenase fromChemical science · 2023Article
- Structural Insight into the Catalytic Mechanisms of an L-Sorbosone Dehydrogenase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Effects of thermal acclimation on the proteome of the planarian Crenobia alpina from an alpine freshwater spring.The Journal of experimental biology · 2022Article
- Characterization of Two Dehydrogenases fromToxins · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Succinic semialdehyde dehydrogenase (SSADH) is involved in the final degradation step of the inhibitory neurotransmitter gamma-aminobutyric acid by converting succinic semialdehyde to succinic acid in the mitochondrial matrix. SSADH deficiency, a rare autosomal recessive disease, exhibits variable clinical phenotypes, including psychomotor retardation, language delay, behaviour disturbance and convulsions. Here, we present crystal structures of both the oxidized and reduced forms of human SSADH. Interestingly, the structures show that the catalytic loop of the enzyme undergoes large structural changes depending on the redox status of the environment, which is mediated by a reversible disulphide bond formation between a catalytic Cys340 and an adjacent Cys342 residues located on the loop. Subsequent in vivo and in vitro studies reveal that the 'dynamic catalytic loop' confers a response to reactive oxygen species and changes in redox status, indicating that the redox-switch modulation could be a physiological control mechanism of human SSADH. Structural basis for the substrate specificity of the enzyme and the impact of known missense point mutations associated with the disease pathogenesis are presented as well.
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