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PDBsum entry 4bnt

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
4bnt
Jmol
Contents
Protein chains
240 a.a.
Ligands
36E ×2
Waters ×119
PDB id:
4bnt
Name: Oxidoreductase
Title: Crystal structure of 3-oxoacyl-(acyl-carrier-protein) reduct (fabg) from pseudomonas aeruginosa in complex with 2-(trifluoromethyl)-1h-benzimidazole at 2.3a resolution
Structure: 3-oxoacyl-[acyl-carrier-protein] reductase fabg. Chain: a, b, c, d. Synonym: 3-oxoacyl-acyl-carrier-protein reductase, 3-ketoac carrier protein reductase, beta-ketoacyl-acyl carrier prot reductase, beta-ketoacyl-acp reductase, 3-oxoacyl-acp redu engineered: yes
Source: Pseudomonas aeruginosa. Organism_taxid: 208964. Strain: pao1. Atcc: 47085. Expressed in: escherichia coli. Expression_system_taxid: 469008.
Resolution:
2.30Å     R-factor:   0.193     R-free:   0.236
Authors: C.D.Cukier,R.Schnell,Y.Lindqvist,G.Schneider
Key ref: C.D.Cukier et al. (2013). Discovery of an allosteric inhibitor binding site in 3-Oxo-acyl-ACP reductase from Pseudomonas aeruginosa. ACS Chem Biol, 8, 2518-2527. PubMed id: 24015914 DOI: 10.1021/cb4005063
Date:
17-May-13     Release date:   18-Sep-13    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
O54438  (FABG_PSEAE) -  3-oxoacyl-[acyl-carrier-protein] reductase FabG
Seq:
Struc:
247 a.a.
240 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.100  - 3-oxoacyl-[acyl-carrier-protein] reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP+ = 3-oxoacyl-[acyl- carrier-protein] + NADPH
(3R)-3-hydroxyacyl-[acyl-carrier-protein]
+ NADP(+)
= 3-oxoacyl-[acyl- carrier-protein]
+ NADPH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   6 terms 
  Biochemical function     oxidoreductase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1021/cb4005063 ACS Chem Biol 8:2518-2527 (2013)
PubMed id: 24015914  
 
 
Discovery of an allosteric inhibitor binding site in 3-Oxo-acyl-ACP reductase from Pseudomonas aeruginosa.
C.D.Cukier, A.G.Hope, A.A.Elamin, L.Moynie, R.Schnell, S.Schach, H.Kneuper, M.Singh, J.H.Naismith, Y.Lindqvist, D.W.Gray, G.Schneider.
 
  ABSTRACT  
 
3-Oxo-acyl-acyl carrier protein (ACP) reductase (FabG) plays a key role in the bacterial fatty acid synthesis II system in pathogenic microorganisms, which has been recognized as a potential drug target. FabG catalyzes reduction of a 3-oxo-acyl-ACP intermediate during the elongation cycle of fatty acid biosynthesis. Here, we report gene deletion experiments that support the essentiality of this gene in P. aeruginosa and the identification of a number of small molecule FabG inhibitors with IC50 values in the nanomolar to low micromolar range and good physicochemical properties. Structural characterization of 16 FabG-inhibitor complexes by X-ray crystallography revealed that the compounds bind at a novel allosteric site located at the FabG subunit-subunit interface. Inhibitor binding relies primarily on hydrophobic interactions, but specific hydrogen bonds are also observed. Importantly, the binding cavity is formed upon complex formation and therefore would not be recognized by virtual screening approaches. The structure analysis further reveals that the inhibitors act by inducing conformational changes that propagate to the active site, resulting in a displacement of the catalytic triad and the inability to bind NADPH.