5T2U

short chain dehydrogenase/reductase family protein


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Binding of NADP(+) triggers an open-to-closed transition in a mycobacterial FabG beta-ketoacyl-ACP reductase.

Blaise, M.Van Wyk, N.Baneres-Roquet, F.Guerardel, Y.Kremer, L.

(2017) Biochem J 474: 907-921

  • DOI: https://doi.org/10.1042/BCJ20161052
  • Primary Citation of Related Structures:  
    5T2U, 5T2V

  • PubMed Abstract: 

    The ketoacyl-acyl carrier protein (ACP) reductase FabG catalyzes the NADPH/NADH dependent reduction of β-ketoacyl-ACP substrates to β-hydroxyacyl-ACP products, the first reductive step in the fatty acid biosynthesis elongation cycle. FabG proteins are ubiquitous in bacteria and are part of the type II fatty acid synthase system. Mining the Mycobacterium smegmatis genome uncovered several putative FabG-like proteins. Among them, we identified M. smegmatis MSMEG_6753 whose gene was found adjacent to MSMEG_6754 , encoding a recently characterized enoyl-CoA dehydratase, and to MSMEG_6755 , encoding another potential reductase. Recombinantly expressed and purified MSMEG_6753 exhibits ketoacyl reductase activity in the presence of acetoacetyl-CoA and NADPH. This activity was subsequently confirmed by functional complementation studies in a fabG thermosensitive Escherichia coli mutant. Furthermore, comparison of the apo and the NADP + -bound MSMEG_6753 crystal structures showed that cofactor binding induces a closed conformation of the protein. A Δ MSMEG_6753 deletion mutant could be generated in M. smegmatis , indicating that this gene is dispensable for mycobacterial growth. Overall, these results showcase the diversity of FabG-like proteins in mycobacteria and new structural features regarding the catalytic mechanism of this important family of enzymes that may be of importance for the rational design of specific FabG inhibitors.


  • Organizational Affiliation

    Centre d'étude d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), Université de Montpellier, CNRS, FRE 3689, 34293 Montpellier, France mickael.blaise@cpbs.cnrs.fr laurent.kremer@cpbs.cnrs.fr.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Oxidoreductase, short chain dehydrogenase/reductase family protein
A, B, C, D
248Mycolicibacterium smegmatis MC2 155Mutation(s): 0 
Gene Names: MSMEG_6753MSMEI_6571
UniProt
Find proteins for A0R723 (Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155))
Explore A0R723 
Go to UniProtKB:  A0R723
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0R723
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.218 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.165 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.01α = 90
b = 116.11β = 90
c = 132.87γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-02-15
    Type: Initial release
  • Version 1.1: 2017-03-22
    Changes: Database references
  • Version 1.2: 2024-01-17
    Changes: Data collection, Database references, Refinement description