2W8Q
The crystal structure of human SSADH in complex with SSA.
Summary for 2W8Q
| Entry DOI | 10.2210/pdb2w8q/pdb |
| Related | 2W8N 2W8O 2W8P 2W8R |
| Descriptor | SUCCINATE-SEMIALDEHYDE DEHYDROGENASE, MITOCHONDRIAL, SULFATE ION, GLYCEROL, ... (5 entities in total) |
| Functional Keywords | mitochondrion, dehydrogenase, oxidoreductase, transit peptide, disease mutation, ssa, nad, ssadh, polymorphism, mitochondria |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Mitochondrion: P51649 |
| Total number of polymer chains | 1 |
| Total formula weight | 53425.43 |
| Authors | Kim, Y.-G.,Kim, K.-J. (deposition date: 2009-01-19, release date: 2009-06-09, Last modification date: 2024-05-08) |
| Primary citation | Kim, Y.-G.,Lee, S.,Kwon, O.-S.,Park, S.-Y.,Lee, S.-J.,Park, B.-J.,Kim, K.-J. Redox-Switch Modulation of Human Ssadh by Dynamic Catalytic Loop. Embo J., 28:959-, 2009 Cited by PubMed 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. PubMed: 19300440DOI: 10.1038/EMBOJ.2009.40 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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