PMID- 20174634
OWN - NLM
STAT- MEDLINE
DCOM- 20100930
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 5
IP  - 2
DP  - 2010 Feb 18
TI  - The X-ray crystal structure of Escherichia coli succinic semialdehyde 
      dehydrogenase; structural insights into NADP+/enzyme interactions.
PG  - e9280
LID - 10.1371/journal.pone.0009280 [doi]
LID - e9280
AB  - BACKGROUND: In mammals succinic semialdehyde dehydrogenase (SSADH) plays an 
      essential role in the metabolism of the inhibitory neurotransmitter 
      gamma-aminobutyric acid (GABA) to succinic acid (SA). Deficiency of SSADH in 
      humans results in elevated levels of GABA and gamma-Hydroxybutyric acid (GHB), 
      which leads to psychomotor retardation, muscular hypotonia, non-progressive 
      ataxia and seizures. In Escherichia coli, two genetically distinct forms of 
      SSADHs had been described that are essential for preventing accumulation of toxic 
      levels of succinic semialdehyde (SSA) in cells. METHODOLOGY/PRINCIPAL FINDINGS: 
      Here we structurally characterise SSADH encoded by the E coli gabD gene by X-ray 
      crystallographic studies and compare these data with the structure of human 
      SSADH. In the E. coli SSADH structure, electron density for the complete NADP+ 
      cofactor in the binding sites is clearly evident; these data in particular 
      revealing how the nicotinamide ring of the cofactor is positioned in each active 
      site. CONCLUSIONS/SIGNIFICANCE: Our structural data suggest that a deletion of 
      three amino acids in E. coli SSADH permits this enzyme to use NADP+, whereas in 
      contrast the human enzyme utilises NAD+. Furthermore, the structure of E. coli 
      SSADH gives additional insight into human mutations that result in disease.
FAU - Langendorf, Christopher G
AU  - Langendorf CG
AD  - Department of Biochemistry and Molecular Biology, Monash University, Clayton 
      Campus, Melbourne, Victoria, Australia.
FAU - Key, Trevor L G
AU  - Key TL
FAU - Fenalti, Gustavo
AU  - Fenalti G
FAU - Kan, Wan-Ting
AU  - Kan WT
FAU - Buckle, Ashley M
AU  - Buckle AM
FAU - Caradoc-Davies, Tom
AU  - Caradoc-Davies T
FAU - Tuck, Kellie L
AU  - Tuck KL
FAU - Law, Ruby H P
AU  - Law RH
FAU - Whisstock, James C
AU  - Whisstock JC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100218
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Escherichia coli Proteins)
RN  - 53-59-8 (NADP)
RN  - EC 1.2.1.24 (Succinate-Semialdehyde Dehydrogenase)
RN  - EC 1.2.1.24 (gabD protein, E coli)
SB  - IM
MH  - Animals
MH  - Binding Sites/genetics
MH  - *Catalytic Domain
MH  - Crystallography, X-Ray
MH  - Escherichia coli Proteins/*chemistry/genetics/metabolism
MH  - Kinetics
MH  - Models, Molecular
MH  - Mutation
MH  - NADP/*chemistry/metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - Substrate Specificity
MH  - Succinate-Semialdehyde Dehydrogenase/*chemistry/genetics/metabolism
PMC - PMC2823781
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2010/02/23 06:00
MHDA- 2010/10/01 06:00
PMCR- 2010/02/18
CRDT- 2010/02/23 06:00
PHST- 2009/10/23 00:00 [received]
PHST- 2010/01/23 00:00 [accepted]
PHST- 2010/02/23 06:00 [entrez]
PHST- 2010/02/23 06:00 [pubmed]
PHST- 2010/10/01 06:00 [medline]
PHST- 2010/02/18 00:00 [pmc-release]
AID - 09-PONE-RA-13750R1 [pii]
AID - 10.1371/journal.pone.0009280 [doi]
PST - epublish
SO  - PLoS One. 2010 Feb 18;5(2):e9280. doi: 10.1371/journal.pone.0009280.