3PJF

Structure of ENR G93V mutant-NAD+-triclosan complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 

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This is version 1.2 of the entry. See complete history


Literature

Structural basis of triclosan resistance

Jiten Singh, N.Shin, D.G.Lee, H.M.Kim, H.T.Chang, H.J.Cho, J.M.Kim, K.S.Ro, S.

(2011) J Struct Biol 174: 173-179

  • DOI: https://doi.org/10.1016/j.jsb.2010.11.008
  • Primary Citation of Related Structures:  
    3PJD, 3PJE, 3PJF

  • PubMed Abstract: 

    Triclosan (5-chloro-2-(2,4-dichloro-phenoxy)-phenol, TCL) is a well known inhibitor against enoyl-acyl carrier protein reductase (ENR), an enzyme critical for cell-wall synthesis of bacteria. The inhibitory concentration at 50% inhibition (IC(50)) of TCL against the Escherichia coli ENR is 150nM for wild type (WT), 380, 470 and 68,500nM for Ala, Ser and Val mutants, respectively. To understand this high TCL resistance in the G93V mutant, we obtained the crystal structures of mutated ENRs complexed with TCL and NAD(+). The X-ray structural analysis along with the ab initio calculations and molecular dynamics simulations explains the serious consequence in the G93V mutant complex. The major interactions around TCL due to the aromatic(cation)-aromatic and hydrogen bonding interactions are found to be conserved both in WT and mutant complexes. Thus, the overall structural change of protein is minimal except that a flexible α-helical turn around TCL is slightly pushed away due to the presence of the bulky valine group. However, TCL shows substantial edge-to-face aromatic (π)-interactions with both the flexible R192-F203 region and the residues in the close vicinity of G93. The weakening of some edge-to-face aromatic interactions around TCL in the G93V mutant results in serious resistance to TCL. This understanding is beneficial to design new generation of antibiotics which will effectively act on the mutant ENRs.


  • Organizational Affiliation

    Center for Superfunctional Materials, Department of Chemistry, Pohang University of Science and Technology, Pohang 780-790, Republic of Korea.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Enoyl-[acyl-carrier-protein] reductase [NADH]
A, B
270Escherichia coli K-12Mutation(s): 1 
Gene Names: ENVMfabI
EC: 1.3.1.9
UniProt
Find proteins for P0AEK4 (Escherichia coli (strain K12))
Explore P0AEK4 
Go to UniProtKB:  P0AEK4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP0AEK4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
TCL Binding MOAD:  3PJF IC50: 6.85e+4 (nM) from 1 assay(s)
BindingDB:  3PJF IC50: min: 5, max: 900 (nM) from 3 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.219 
  • Space Group: P 61 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 79.484α = 90
b = 79.484β = 90
c = 323.266γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
PHASESphasing
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-20
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description