2w8r | pdb_00002w8r

The crystal structure of human SSADH in complex with NAD+

spinqualitylabelsall models 2w8r, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2w8r is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: ADP, GOL, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SSDH_HUMAN Defects in ALDH5A1 are the cause of succinate semialdehyde dehydrogenase deficiency (SSADH deficiency) [MIM:271980. SSADH deficiency is a rare inborn error in the metabolism of 4-aminobutyric acid (GABA) which leads to accumulation of 4-hydroxybutyric acid in physiologic fluids of patients. The disease is characterized by severe ataxia and by mildly retarded psychomotor development. Function SSDH_HUMAN Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. Redox-switch modulation of human SSADH by dynamic catalytic loop.,Kim YG, Lee S, Kwon OS, Park SY, Lee SJ, Park BJ, Kim KJ EMBO J. 2009 Apr 8;28(7):959-68. Epub 2009 Mar 19. PMID:19300440 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aldehyde dehydrogenase 3D structures Succinate-semialdehyde dehydrogenase

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