3EFV

Crystal Structure of a Putative Succinate-Semialdehyde Dehydrogenase from Salmonella typhimurium LT2 with bound NAD


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.185 
  • R-Value Work: 0.159 
  • R-Value Observed: 0.160 

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This is version 1.4 of the entry. See complete history


Literature

Structure and activity of the NAD(P)(+) -dependent succinate semialdehyde dehydrogenase YneI from Salmonella typhimurium.

Zheng, H.Beliavsky, A.Tchigvintsev, A.Brunzelle, J.S.Brown, G.Flick, R.Evdokimova, E.Wawrzak, Z.Mahadevan, R.Anderson, W.F.Savchenko, A.Yakunin, A.F.

(2013) Proteins 81: 1031-1041

  • DOI: https://doi.org/10.1002/prot.24227
  • Primary Citation of Related Structures:  
    3EFV, 3ETF

  • PubMed Abstract: 

    Aldehyde dehydrogenases are found in all organisms and play an important role in the metabolic conversion and detoxification of endogenous and exogenous aldehydes. Genomes of many organisms including Escherichia coli and Salmonella typhimurium encode two succinate semialdehyde dehydrogenases with low sequence similarity and different cofactor preference (YneI and GabD). Here, we present the crystal structure and biochemical characterization of the NAD(P)(+)-dependent succinate semialdehyde dehydrogenase YneI from S. typhimurium. This enzyme shows high activity and affinity toward succinate semialdehyde and exhibits substrate inhibition at concentrations of SSA higher than 0.1 mM. YneI can use both NAD(+) and NADP(+) as cofactors, although affinity to NAD(+) is 10 times higher. High resolution crystal structures of YneI were solved in a free state (1.85 Å) and in complex with NAD(+) (1.90 Å) revealing a two domain protein with the active site located in the interdomain interface. The NAD(+) molecule is bound in the long channel with its nicotinamide ring positioned close to the side chain of the catalytic Cys268. Site-directed mutagenesis demonstrated that this residue, as well as the conserved Trp136, Glu365, and Asp426 are important for activity of YneI, and that the conserved Lys160 contributes to the enzyme preference to NAD(+) . Our work has provided further insight into the molecular mechanisms of substrate selectivity and activity of succinate semialdehyde dehydrogenases.


  • Organizational Affiliation

    Department of Chemical Engineering and Applied Chemistry, Banting and Best Department of Medical Research, University of Toronto, Toronto, Ontario, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Putative succinate-semialdehyde dehydrogenase
A, B, C, D
462Salmonella enterica subsp. enterica serovar TyphimuriumMutation(s): 0 
Gene Names: yneISTM1524
EC: 1.2.1
UniProt
Find proteins for Q8ZPI3 (Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720))
Explore Q8ZPI3 
Go to UniProtKB:  Q8ZPI3
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8ZPI3
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 133.826α = 90
b = 133.826β = 90
c = 245.276γ = 120
Software Package:
Software NamePurpose
BLU-MAXdata collection
SHELXDphasing
SHARPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Entry History 

Revision History  (Full details and data files)

  • Version 1.0: 2008-11-04
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-12-14
    Changes: Structure summary
  • Version 1.3: 2012-12-19
    Changes: Database references
  • Version 1.4: 2013-06-12
    Changes: Database references