PDBsum entry 2w8q

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protein ligands links
Oxidoreductase PDB id
Protein chain
485 a.a. *
SO4 ×9
GOL ×2
Waters ×66
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: The crystal structure of human ssadh in complex with ssa.
Structure: Succinate-semialdehyde dehydrogenase, mitochondrial. Chain: a. Fragment: residues 49-535. Synonym: NAD(+)-dependent succinic semialdehyde dehydrogenase, aldehyde dehydrogenase family 5 member a1, succinic semialdehyde dehydrogenase. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.40Å     R-factor:   0.224     R-free:   0.253
Authors: Y.-G.Kim,K.-J.Kim
Key ref: Y.G.Kim et al. (2009). Redox-switch modulation of human SSADH by dynamic catalytic loop. EMBO J, 28, 959-968. PubMed id: 19300440
19-Jan-09     Release date:   09-Jun-09    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P51649  (SSDH_HUMAN) -  Succinate-semialdehyde dehydrogenase, mitochondrial
535 a.a.
485 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Succinate-semialdehyde dehydrogenase (NAD(+)).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Succinate semialdehyde + NAD+ + H2O = succinate + NADH
Succinate semialdehyde
Bound ligand (Het Group name = SIN)
corresponds exactly
+ NAD(+)
+ H(2)O
= succinate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   2 terms 
  Biological process     metabolic process   21 terms 
  Biochemical function     oxidoreductase activity     6 terms  


EMBO J 28:959-968 (2009)
PubMed id: 19300440  
Redox-switch modulation of human SSADH by dynamic catalytic loop.
Y.G.Kim, S.Lee, O.S.Kwon, S.Y.Park, S.J.Lee, B.J.Park, K.J.Kim.
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.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21303655 Carvalho, Y.Ling, C.Shen, J.D.Warren, and K.Y.Rhee (2011).
On the chemical mechanism of succinic semialdehyde dehydrogenase (GabD1) from Mycobacterium tuberculosis.
  Arch Biochem Biophys, 509, 90-99.  
  21438145 L.Siggberg, A.Mustonen, R.Schuit, G.S.Salomons, B.Roos, K.M.Gibson, C.Jakobs, J.Ignatius, and S.Knuutila (2011).
Familial 6p22.2 duplication associates with mild developmental delay and increased SSADH activity.
  Am J Med Genet B Neuropsychiatr Genet, 156, 448-453.  
20174634 C.G.Langendorf, T.L.Key, G.Fenalti, W.T.Kan, A.M.Buckle, T.Caradoc-Davies, K.L.Tuck, R.H.Law, and J.C.Whisstock (2010).
The X-ray crystal structure of Escherichia coli succinic semialdehyde dehydrogenase; structural insights into NADP+/enzyme interactions.
  PLoS One, 5, e9280.
PDB code: 3jz4
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