3LT0

Enoyl-ACP Reductase from Plasmodium falciparum (PfENR) in complex with triclosan variant T1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

X-ray crystallographic analysis of the complexes of enoyl acyl carrier protein reductase of Plasmodium falciparum with triclosan variants to elucidate the importance of different functional groups in enzyme inhibition

Maity, K.Bhargav, S.P.Sankaran, B.Surolia, N.Surolia, A.Suguna, K.

(2010) IUBMB Life 62: 467-476

  • DOI: https://doi.org/10.1002/iub.327
  • Primary Citation of Related Structures:  
    3LSY, 3LT0, 3LT1, 3LT2, 3LT4

  • PubMed Abstract: 

    Triclosan, a well-known inhibitor of Enoyl Acyl Carrier Protein Reductase (ENR) from several pathogenic organisms, is a promising lead compound to design effective drugs. We have solved the X-ray crystal structures of Plasmodium falciparum ENR in complex with triclosan variants having different substituted and unsubstituted groups at different key functional locations. The structures revealed that 4 and 2' substituted compounds have more interactions with the protein, cofactor, and solvents when compared with triclosan. New water molecules were found to interact with some of these inhibitors. Substitution at the 2' position of triclosan caused the relocation of a conserved water molecule, leading to an additional hydrogen bond with the inhibitor. This observation can help in conserved water-based inhibitor design. 2' and 4' unsubstituted compounds showed a movement away from the hydrophobic pocket to compensate for the interactions made by the halogen groups of triclosan. This compound also makes additional interactions with the protein and cofactor which compensate for the lost interactions due to the unsubstitution at 2' and 4'. In cell culture, this inhibitor shows less potency, which indicates that the chlorines at 2' and 4' positions increase the ability of the inhibitor to cross multilayered membranes. This knowledge helps us to modify the different functional groups of triclosan to get more potent inhibitors.


  • Organizational Affiliation

    Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Enoyl-ACP reductase
A, B
329Plasmodium falciparumMutation(s): 0 
Gene Names: FabI
EC: 1.3.1.9
UniProt
Find proteins for Q9BJJ9 (Plasmodium falciparum)
Explore Q9BJJ9 
Go to UniProtKB:  Q9BJJ9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BJJ9
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
FT1 Binding MOAD:  3LT0 Ki: 180 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.96 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.174 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 131.063α = 90
b = 131.063β = 90
c = 82.919γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-06-16
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2012-02-29
    Changes: Atomic model
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description