PDBsum entry 4fw8

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Oxidoreductase PDB id
Protein chains
427 a.a.
NAI ×4
Waters ×216
PDB id:
Name: Oxidoreductase
Title: Crystal structure of fabg4 complexed with coenzyme nadh
Structure: 3-oxoacyl-(acyl-carrier-protein) reductase. Chain: a, b, c, d. Synonym: ketoreductase, probable 3-oxoacyl-[acyl-carrier pr reductase fabg4 (3-ketoacyl-acyl carrier protein reductase) engineered: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 83332. Strain: h37rv. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.79Å     R-factor:   0.166     R-free:   0.238
Authors: D.Dutta,S.Bhattacharyya,A.K.Das
Key ref: D.Dutta et al. (2013). Crystal structure of hexanoyl-CoA bound to β-ketoacyl reductase FabG4 of Mycobacterium tuberculosis. Biochem J, 450, 127-139. PubMed id: 23163771 DOI: 10.1042/BJ20121107
30-Jun-12     Release date:   28-Nov-12    
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Protein chains
Pfam   ArchSchema ?
O53665  (O53665_MYCTU) -  3-oxoacyl-(Acyl-carrier-protein) reductase
454 a.a.
427 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - 3-oxoacyl-[acyl-carrier-protein] reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (3R)-3-hydroxyacyl-[acyl-carrier-protein] + NADP+ = 3-oxoacyl-[acyl- carrier-protein] + NADPH
+ NADP(+)
= 3-oxoacyl-[acyl- carrier-protein]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   4 terms 
  Biological process     metabolic process   5 terms 
  Biochemical function     nucleotide binding     3 terms  


DOI no: 10.1042/BJ20121107 Biochem J 450:127-139 (2013)
PubMed id: 23163771  
Crystal structure of hexanoyl-CoA bound to β-ketoacyl reductase FabG4 of Mycobacterium tuberculosis.
D.Dutta, S.Bhattacharyya, A.Roychowdhury, R.Biswas, A.K.Das.
FabGs, or β-oxoacyl reductases, are involved in fatty acid synthesis. The reaction entails NADPH/NADH-mediated conversion of β-oxoacyl-ACP (acyl-carrier protein) into β-hydroxyacyl-ACP. HMwFabGs (high-molecular-weight FabG) form a phylogenetically separate group of FabG enzymes. FabG4, an HMwFabG from Mycobacterium tuberculosis, contains two distinct domains, an N-terminal 'flavodoxintype' domain and a C-terminal oxoreductase domain. The catalytically active C-terminal domain utilizes NADH to reduce β-oxoacyl-CoA to β-hydroxyacyl-CoA. In the present study the crystal structures of the FabG4-NADH binary complex and the FabG4-NAD+-hexanoyl-CoA ternary complex have been determined to understand the substrate specificity and catalytic mechanism of FabG4. This is the first report to demonstrate how FabG4 interacts with its coenzyme NADH and hexanoyl-CoA that mimics an elongating fattyacyl chain covalently linked with CoA. Structural analysis shows that the binding of hexanoyl-CoA within the active site cavity of FabG significantly differs from that of the C16 fattyacyl substrate bound to mycobacterial FabI [InhA (enoyl-ACP reductase)]. The ternary complex reveals that both loop I and loop II interact with the phosphopantetheine moiety of CoA or ACP to align the covalently linked fattyacyl substrate near the active site. Structural data ACP inhibition studies indicate that FabG4 can accept both CoA- and ACP-based fattyacyl substrates. We have also shown that in the FabG4 dimer Arg146 and Arg445 of one monomer interact with the C-terminus of the second monomer to play pivotal role in substrate association and catalysis.