2F3X | pdb_00002f3x

Crystal structure of FapR (in complex with effector)- a global regulator of fatty acid biosynthesis in B. subtilis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free: 
    0.226 (Depositor), 0.260 (DCC) 
  • R-Value Work: 
    0.187 (Depositor), 0.230 (DCC) 
  • R-Value Observed: 
    0.190 (Depositor) 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structural basis of lipid biosynthesis regulation in Gram-positive bacteria.

Schujman, G.E.Guerin, M.Buschiazzo, A.Schaeffer, F.Llarrull, L.I.Reh, G.Vila, A.J.Alzari, P.M.de Mendoza, D.

(2006) EMBO J 25: 4074-4083

  • DOI: https://doi.org/10.1038/sj.emboj.7601284
  • Primary Citation of Related Structures:  
    2F3X, 2F41

  • PubMed Abstract: 

    Malonyl-CoA is an essential intermediate in fatty acid synthesis in all living cells. Here we demonstrate a new role for this molecule as a global regulator of lipid homeostasis in Gram-positive bacteria. Using in vitro transcription and binding studies, we demonstrate that malonyl-CoA is a direct and specific inducer of Bacillus subtilis FapR, a conserved transcriptional repressor that regulates the expression of several genes involved in bacterial fatty acid and phospholipid synthesis. The crystal structure of the effector-binding domain of FapR reveals a homodimeric protein with a thioesterase-like 'hot-dog' fold. Binding of malonyl-CoA promotes a disorder-to-order transition, which transforms an open ligand-binding groove into a long tunnel occupied by the effector molecule in the complex. This ligand-induced modification propagates to the helix-turn-helix motifs, impairing their productive association for DNA binding. Structure-based mutations that disrupt the FapR-malonyl-CoA interaction prevent DNA-binding regulation and result in a lethal phenotype in B. subtilis, suggesting this homeostatic signaling pathway as a promising target for novel chemotherapeutic agents against Gram-positive pathogens.


  • Organizational Affiliation

    Instituto de Biología Molecular y Celular de Rosario (IBR), Universidad Nacional de Rosario, Rosario, Argentina.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Transcription factor fapR
A, B
157Bacillus subtilisMutation(s): 0 
Gene Names: fapR
UniProt
Find proteins for O34835 (Bacillus subtilis (strain 168))
Explore O34835 
Go to UniProtKB:  O34835
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO34835
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.10 Å
  • R-Value Free:  0.226 (Depositor), 0.260 (DCC) 
  • R-Value Work:  0.187 (Depositor), 0.230 (DCC) 
  • R-Value Observed: 0.190 (Depositor) 
Space Group: P 41 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 89.441α = 90
b = 89.441β = 90
c = 162.166γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
REFMACrefinement
PDB_EXTRACTdata extraction
MOSFLMdata reduction
CCP4data scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-10-31
    Type: Initial release
  • Version 1.1: 2008-05-05
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2024-02-14
    Changes: Data collection, Database references, Derived calculations