1VRW

Crystal structure analysis of plasmodium falciparum enoyl-acyl-carrier-protein reductase with nadh


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structural Elucidation of the Specificity of the Antibacterial Agent Triclosan for Malarial Enoyl Acyl Carrier Protein Reductase

Perozzo, R.Kuo, M.Sidhu, A.S.Valiyaveettil, J.T.Bittman, R.Jacobs Jr., W.R.Fidock, D.A.Sacchettini, J.C.

(2002) J Biol Chem 277: 13106-13114

  • DOI: https://doi.org/10.1074/jbc.M112000200
  • Primary Citation of Related Structures:  
    1NHG, 1NHW, 1NNU, 1VRW

  • PubMed Abstract: 

    The human malaria parasite Plasmodium falciparum synthesizes fatty acids using a type II pathway that is absent in humans. The final step in fatty acid elongation is catalyzed by enoyl acyl carrier protein reductase, a validated antimicrobial drug target. Here, we report the cloning and expression of the P. falciparum enoyl acyl carrier protein reductase gene, which encodes a 50-kDa protein (PfENR) predicted to target to the unique parasite apicoplast. Purified PfENR was crystallized, and its structure resolved as a binary complex with NADH, a ternary complex with triclosan and NAD(+), and as ternary complexes bound to the triclosan analogs 1 and 2 with NADH. Novel structural features were identified in the PfENR binding loop region that most closely resembled bacterial homologs; elsewhere the protein was similar to ENR from the plant Brassica napus (root mean square for Calphas, 0.30 A). Triclosan and its analogs 1 and 2 killed multidrug-resistant strains of intra-erythrocytic P. falciparum parasites at sub to low micromolar concentrations in vitro. These data define the structural basis of triclosan binding to PfENR and will facilitate structure-based optimization of PfENR inhibitors.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ENOYL-ACYL CARRIER REDUCTASE
A, B
336Plasmodium falciparumMutation(s): 0 
EC: 1.3.1.9
UniProt
Find proteins for Q9BH77 (Plasmodium falciparum)
Explore Q9BH77 
Go to UniProtKB:  Q9BH77
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BH77
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAI
Query on NAI

Download Ideal Coordinates CCD File 
C [auth A],
D [auth B]
1,4-DIHYDRONICOTINAMIDE ADENINE DINUCLEOTIDE
C21 H29 N7 O14 P2
BOPGDPNILDQYTO-NNYOXOHSSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.176 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 133.28α = 90
b = 133.28β = 90
c = 83.828γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
CNSrefinement
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-07-05
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2013-10-30
    Changes: Non-polymer description
  • Version 1.4: 2018-04-04
    Changes: Data collection
  • Version 1.5: 2023-12-27
    Changes: Data collection, Database references, Derived calculations