2W8O: The Crystal Structure Of The Reduced Form Of Human Ssadh

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.
PDB ID: 2W8ODownload
MMDB ID: 73100
PDB Deposition Date: 2009/1/19
Updated in MMDB: 2013/08
Experimental Method:
x-ray diffraction
Resolution: 3.4  Å
Source Organism:
Similar Structures:
Biological Unit for 2W8O: dodecameric; determined by author and by software (PQS)
Molecular Components in 2W8O
Label Count Molecule
Proteins (12 molecules)
Succinic Semialdehyde Dehydrogenase Mitochondrial(Gene symbol: ALDH5A1)
Molecule annotation
Chemicals (120 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB