2W8Q

The crystal structure of human SSADH in complex with SSA.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.224 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Redox-Switch Modulation of Human Ssadh by Dynamic Catalytic Loop.

Kim, Y.-G.Lee, S.Kwon, O.-S.Park, S.-Y.Lee, S.-J.Park, B.-J.Kim, K.-J.

(2009) EMBO J 28: 959

  • DOI: https://doi.org/10.1038/emboj.2009.40
  • Primary Citation of Related Structures:  
    2W8N, 2W8O, 2W8P, 2W8Q, 2W8R

  • 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.


  • Organizational Affiliation

    Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang, Kyungbuk, Republic of Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SUCCINATE-SEMIALDEHYDE DEHYDROGENASE, MITOCHONDRIAL487Homo sapiensMutation(s): 1 
EC: 1.2.1.24
UniProt & NIH Common Fund Data Resources
Find proteins for P51649 (Homo sapiens)
Explore P51649 
Go to UniProtKB:  P51649
PHAROS:  P51649
GTEx:  ENSG00000112294 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP51649
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SIN
Query on SIN

Download Ideal Coordinates CCD File 
M [auth A]SUCCINIC ACID
C4 H6 O4
KDYFGRWQOYBRFD-UHFFFAOYSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A]
C [auth A]
D [auth A]
E [auth A]
F [auth A]
B [auth A],
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
GOL
Query on GOL

Download Ideal Coordinates CCD File 
K [auth A],
L [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.253 
  • R-Value Work: 0.224 
  • R-Value Observed: 0.224 
  • Space Group: F 4 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 265.4α = 90
b = 265.4β = 90
c = 265.4γ = 90
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-06-09
    Type: Initial release
  • Version 1.1: 2013-08-07
    Changes: Derived calculations, Non-polymer description, Other, Source and taxonomy, Structure summary, Version format compliance