5HEV

Crystal Structure of the beryllofluoride-activated LiaR from Enterococcus faecium


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.19 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

An Adaptive Mutation in Enterococcus faecium LiaR Associated with Antimicrobial Peptide Resistance Mimics Phosphorylation and Stabilizes LiaR in an Activated State.

Davlieva, M.Tovar-Yanez, A.DeBruler, K.Leonard, P.G.Zianni, M.R.Arias, C.A.Shamoo, Y.

(2016) J Mol Biol 428: 4503-4519

  • DOI: https://doi.org/10.1016/j.jmb.2016.09.016
  • Primary Citation of Related Structures:  
    5HEV

  • PubMed Abstract: 

    The cyclic antimicrobial lipopeptide daptomycin (DAP) triggers the LiaFSR membrane stress response pathway in enterococci and many other Gram-positive organisms. LiaR is the response regulator that, upon phosphorylation, binds in a sequence-specific manner to DNA to regulate transcription in response to membrane stress. In clinical settings, non-susceptibility to DAP by Enterococcus faecium is correlated frequently with a mutation in LiaR of Trp73 to Cys (LiaR W73C ). We have determined the structure of the activated E. faecium LiaR protein at 3.2Å resolution and, in combination with solution studies, show that the activation of LiaR induces the formation of a LiaR dimer that increases LiaR affinity at least 40-fold for the extended regulatory regions upstream of the liaFSR and liaXYZ operons. In vitro, LiaR W73C induces phosphorylation-independent dimerization of LiaR and provides a biochemical basis for non-susceptibility to DAP by the upregulation of the LiaFSR regulon. A comparison of the E. faecalis LiaR, E. faecium LiaR, and the LiaR homolog from Staphylococcus aureus (VraR) and the mutations associated with DAP resistance suggests that physicochemical properties such as oligomerization state and DNA specificity, although tuned to the biology of each organism, share some features that could be targeted for new antimicrobials.


  • Organizational Affiliation

    Department of Biosciences, Rice University, Houston, TX 77005, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Response regulator protein VraRA,
B [auth F],
C [auth B],
D [auth C]
210Enterococcus faecium SD3B-2Mutation(s): 0 
Gene Names: D357_01142
UniProt
Find proteins for S4FAU8 (Enterococcus faecium SD3B-2)
Explore S4FAU8 
Go to UniProtKB:  S4FAU8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupS4FAU8
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.19 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.223 
  • Space Group: P 31
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 68.032α = 90
b = 68.032β = 90
c = 276.949γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
PHASERphasing
PDB_EXTRACTdata extraction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesR01AI080714

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-16
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence, Derived calculations
  • Version 1.2: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description