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PDBsum entry 4igf

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protein ligands Protein-protein interface(s) links
Oxidoreductase/oxidoreductase inhibitor PDB id
4igf
Jmol
Contents
Protein chains
277 a.a.
Ligands
CHV ×2
NAD ×2
GOL ×3
SO4 ×2
Waters ×243
PDB id:
4igf
Name: Oxidoreductase/oxidoreductase inhibitor
Title: Crystal structure of plasmodium falciparum fabi complexed wi inhibitor 3-(4-chloro-2-hydroxyphenoxy)-7-hydroxy-2h-chrome
Structure: Enoyl-acyl carrier reductase. Chain: a, b. Fragment: c-terminal fragment, unp residues 96-432. Engineered: yes
Source: Plasmodium falciparum. Organism_taxid: 36329. Strain: 3d7. Gene: pfenr, pff0730c. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.30Å     R-factor:   0.156     R-free:   0.202
Authors: D.Kostrewa,R.Perozzo
Key ref: F.Belluti et al. (2013). Design, synthesis, and biological and crystallographic evaluation of novel inhibitors of Plasmodium falciparum enoyl-ACP-reductase (PfFabI). J Med Chem, 56, 7516-7526. PubMed id: 24063369 DOI: 10.1021/jm400637m
Date:
17-Dec-12     Release date:   06-Nov-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
C6KSZ2  (C6KSZ2_PLAF7) -  Enoyl-acyl carrier reductase
Seq:
Struc:
432 a.a.
277 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]
Bound ligand (Het Group name = GOL)
matches with 44.44% similarity
+
NAD(+)
Bound ligand (Het Group name = NAD)
corresponds exactly
= trans-2,3-dehydroacyl-[acyl- carrier protein]
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1021/jm400637m J Med Chem 56:7516-7526 (2013)
PubMed id: 24063369  
 
 
Design, synthesis, and biological and crystallographic evaluation of novel inhibitors of Plasmodium falciparum enoyl-ACP-reductase (PfFabI).
F.Belluti, R.Perozzo, L.Lauciello, F.Colizzi, D.Kostrewa, A.Bisi, S.Gobbi, A.Rampa, M.L.Bolognesi, M.Recanatini, R.Brun, L.Scapozza, A.Cavalli.
 
  ABSTRACT  
 
Malaria, a disease of worldwide significance, is responsible for over one million deaths annually. The liver-stage of Plasmodium's life cycle is the first, obligatory, but clinically silent step in malaria infection. The P. falciparum type II fatty acid biosynthesis pathway (PfFAS-II) has been found to be essential for complete liver-stage development and has been regarded as a potential antimalarial target for the development of drugs for malaria prophylaxis and liver-stage eradication. In this paper, new coumarin-based triclosan analogues are reported and their biological profile is explored in terms of inhibitory potency against enzymes of the PfFAS-II pathway. Among the tested compounds, 7 and 8 showed the highest inhibitory potency against Pf enoyl-ACP-reductase (PfFabI), followed by 15 and 3. Finally, we determined the crystal structures of compounds 7 and 11 in complex with PfFabI to identify their mode of binding and to confirm outcomes of docking simulations.