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PDBsum entry 2o50

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protein Protein-protein interface(s) links
Oxidoreductase PDB id
2o50
Jmol
Contents
Protein chains
290 a.a. *
Waters ×11
* Residue conservation analysis
PDB id:
2o50
Name: Oxidoreductase
Title: The crystal structure of toxoplasma gondii enoyl acyl carrie reductase
Structure: Enoyl-acyl carrier reductase. Chain: a, b. Fragment: residues 103-417. Engineered: yes
Source: Toxoplasma gondii. Organism_taxid: 383379. Strain: rh. Gene: enr. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.90Å     R-factor:   0.213     R-free:   0.277
Authors: S.P.Muench,S.T.Prigge,R.Mcleod,J.B.Rafferty,D.W.Rice
Key ref:
S.P.Muench et al. (2007). Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents. Acta Crystallogr D Biol Crystallogr, 63, 328-338. PubMed id: 17327670 DOI: 10.1107/S0907444906053625
Date:
05-Dec-06     Release date:   26-Dec-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q6UCJ9  (Q6UCJ9_TOXGO) -  Enoyl-acyl carrier reductase
Seq:
Struc:
417 a.a.
290 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.3.1.9  - Enoyl-[acyl-carrier-protein] reductase (NADH).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An acyl-[acyl-carrier protein] + NAD+ = a trans-2,3-dehydroacyl-[acyl- carrier protein] + NADH
acyl-[acyl-carrier protein]
+ NAD(+)
= trans-2,3-dehydroacyl-[acyl- carrier protein]
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     enoyl-[acyl-carrier-protein] reductase (NADH) activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1107/S0907444906053625 Acta Crystallogr D Biol Crystallogr 63:328-338 (2007)
PubMed id: 17327670  
 
 
Studies of Toxoplasma gondii and Plasmodium falciparum enoyl acyl carrier protein reductase and implications for the development of antiparasitic agents.
S.P.Muench, S.T.Prigge, R.McLeod, J.B.Rafferty, M.J.Kirisits, C.W.Roberts, E.J.Mui, D.W.Rice.
 
  ABSTRACT  
 
Recent studies have demonstrated that submicromolar concentrations of the biocide triclosan arrest the growth of the apicomplexan parasites Plasmodium falciparum and Toxoplasma gondii and inhibit the activity of the apicomplexan enoyl acyl carrier protein reductase (ENR). The crystal structures of T. gondii and P. falciparum ENR in complex with NAD(+) and triclosan and of T. gondii ENR in an apo form have been solved to 2.6, 2.2 and 2.8 A, respectively. The structures of T. gondii ENR have revealed that, as in its bacterial and plant homologues, a loop region which flanks the active site becomes ordered upon inhibitor binding, resulting in the slow tight binding of triclosan. In addition, the T. gondii ENR-triclosan complex reveals the folding of a hydrophilic insert common to the apicomplexan family that flanks the substrate-binding domain and is disordered in all other reported apicomplexan ENR structures. Structural comparison of the apicomplexan ENR structures with their bacterial and plant counterparts has revealed that although the active sites of the parasite enzymes are broadly similar to those of their bacterial counterparts, there are a number of important differences within the drug-binding pocket that reduce the packing interactions formed with several inhibitors in the apicomplexan ENR enzymes. Together with other significant structural differences, this provides a possible explanation of the lower affinity of the parasite ENR enzyme family for aminopyridine-based inhibitors, suggesting that an effective antiparasitic agent may well be distinct from equivalent antimicrobials.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 The structural formulae of (a) triclosan and (b) (E)-N-methyl-N-(1-methyl-1H-indol-3-ylmethyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-ylacrylamide (compound 29) produced using the program ISIS/Draw.
Figure 4.
Figure 4 2F[obs] - 1F[calc] electron-density maps for (a) PfENR and (b) TgENR contoured at 0.8 produced after initial rigid-body refinement in REFMAC5 (Murshudov et al., 1997[Murshudov, G., Vagin, A. & Dodson, E. (1997). Acta Cryst. D53, 240-255.]). Both NAD^+ and triclosan were omitted from the model during refinement, but are represented in stick format in order to show their unambiguous position in the initial electron-density maps. (c) Stereo diagram of the residues responsible for forming a hydrogen-bonding network to the NAD^+ cofactor in subunit A of TgENR. (d) Stereo diagram of the triclosan-binding site of subunit A of TgENR, with the active-site residues Tyr179, Tyr189, Lys197 and Phe243 labelled. (c) and (d) use the colour scheme yellow, red, blue, green and orange for carbon, oxygen, nitrogen, chlorine and phosphorus, respectively, and were produced in TURBO-FRODO (Roussel et al., 1990[Roussel, A., Fontecilla-Camps, J. C. & Cambillau, C. (1990). Acta Cryst. A46, C66-C67.]).
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2007, 63, 328-338) copyright 2007.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21280175 K.Maity, T.Banerjee, N.Prabakaran, N.Surolia, A.Surolia, and K.Suguna (2011).
Effect of substrate binding loop mutations on the structure, kinetics, and inhibition of enoyl acyl carrier protein reductase from plasmodium falciparum.
  IUBMB Life, 63, 30-41.
PDB codes: 3am3 3am4 3am5
  20559451 C.Ben Mamoun, S.T.Prigge, and H.Vial (2010).
Targeting the Lipid Metabolic Pathways for the Treatment of Malaria.
  Drug Dev Res, 71, 44-55.  
17715365 J.Mazumdar, and B.Striepen (2007).
Make it or take it: fatty acid metabolism of apicomplexan parasites.
  Eukaryot Cell, 6, 1727-1735.  
17875391 P.Gayathri, H.Balaram, and M.R.Murthy (2007).
Structural biology of plasmodial proteins.
  Curr Opin Struct Biol, 17, 744-754.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.