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PDBsum entry 1i2z

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1i2z
Jmol
Contents
Protein chains
257 a.a. *
Ligands
NAD ×2
654 ×2
Waters ×113
* Residue conservation analysis
PDB id:
1i2z
Name: Oxidoreductase
Title: E. Coli enoyl reductase in complex with NAD and brl-12654
Structure: Enoyl-[acyl-carrier-protein] reductase [nadh]. Chain: a, b. Synonym: enoyl-acp reductase. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Tetramer (from PDB file)
Resolution:
2.80Å     R-factor:   0.191     R-free:   0.273
Authors: D.A.Heerding,W.H.Miller,D.J.Payne,C.A.Janson,X.Qiu
Key ref: D.A.Heerding et al. (2001). 1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI). Bioorg Med Chem Lett, 11, 2061-2065. PubMed id: 11514139 DOI: 10.1016/S0960-894X(01)00404-8
Date:
12-Feb-01     Release date:   12-Feb-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0AEK4  (FABI_ECOLI) -  Enoyl-[acyl-carrier-protein] reductase [NADH] FabI
Seq:
Struc:
262 a.a.
257 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(+)
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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   1 term 
  Biological process     metabolic process   10 terms 
  Biochemical function     oxidoreductase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1016/S0960-894X(01)00404-8 Bioorg Med Chem Lett 11:2061-2065 (2001)
PubMed id: 11514139  
 
 
1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI).
D.A.Heerding, G.Chan, W.E.DeWolf, A.P.Fosberry, C.A.Janson, D.D.Jaworski, E.McManus, W.H.Miller, T.D.Moore, D.J.Payne, X.Qiu, S.F.Rittenhouse, C.Slater-Radosti, W.Smith, D.T.Takata, K.S.Vaidya, C.C.Yuan, W.F.Huffman.
 
  ABSTRACT  
 
1,4-Disubstituted imidazole inhibitors of Staphylococcus aureus and Escherichia coli enoyl acyl carrier protein reductase (FabI) have been identified. Crystal structure data shows the inhibitor 1 bound in the enzyme active site of E. coli FabI.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21506178 D.Zhao, J.You, and C.Hu (2011).
Recent progress in coupling of two heteroarenes.
  Chemistry, 17, 5466-5492.  
20131353 G.Kumar, T.Banerjee, N.Kapoor, N.Surolia, and A.Surolia (2010).
SAR and pharmacophore models for the rhodanine inhibitors of Plasmodium falciparum enoyl-acyl carrier protein reductase.
  IUBMB Life, 62, 204-213.  
19282328 C.J.Zheng, M.J.Sohn, and W.G.Kim (2009).
Vinaxanthone, a new FabI inhibitor from Penicillium sp.
  J Antimicrob Chemother, 63, 949-953.  
19734171 K.England, C.am Ende, H.Lu, T.J.Sullivan, N.L.Marlenee, R.A.Bowen, S.E.Knudson, D.L.Knudson, P.J.Tonge, and R.A.Slayden (2009).
Substituted diphenyl ethers as a broad-spectrum platform for the development of chemotherapeutics for the treatment of tularaemia.
  J Antimicrob Chemother, 64, 1052-1061.  
18305197 J.Saito, M.Yamada, T.Watanabe, M.Iida, H.Kitagawa, S.Takahata, T.Ozawa, Y.Takeuchi, and F.Ohsawa (2008).
Crystal structure of enoyl-acyl carrier protein reductase (FabK) from Streptococcus pneumoniae reveals the binding mode of an inhibitor.
  Protein Sci, 17, 691-699.
PDB codes: 2z6i 2z6j
18694482 S.Goh, and L.Good (2008).
Plasmid selection in Escherichia coli using an endogenous essential gene marker.
  BMC Biotechnol, 8, 61.  
17327670 S.P.Muench, S.T.Prigge, R.McLeod, J.B.Rafferty, M.J.Kirisits, C.W.Roberts, E.J.Mui, and D.W.Rice (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.
PDB codes: 2o2s 2o2y 2o50
17420562 S.Takahata, M.Iida, T.Yoshida, K.Kumura, H.Kitagawa, and S.Hoshiko (2007).
Discovery of 4-Pyridone derivatives as specific inhibitors of enoyl-acyl carrier protein reductase (FabI) with antibacterial activity against Staphylococcus aureus.
  J Antibiot (Tokyo), 60, 123-128.  
17323650 C.J.Zheng, M.J.Sohn, and W.G.Kim (2006).
Atromentin and leucomelone, the first inhibitors specific to enoyl-ACP reductase (FabK) of Streptococcus pneumoniae.
  J Antibiot (Tokyo), 59, 808-812.  
16952137 D.Häbich, and F.von Nussbaum (2006).
Platensimycin, a new antibiotic and "superbug challenger" from nature.
  ChemMedChem, 1, 951-954.  
16870790 S.Takahata, M.Iida, Y.Osaki, J.Saito, H.Kitagawa, T.Ozawa, T.Yoshida, and S.Hoshiko (2006).
AG205, a novel agent directed against FabK of Streptococcus pneumoniae.
  Antimicrob Agents Chemother, 50, 2869-2871.  
15105103 L.L.Ling, J.Xian, S.Ali, B.Geng, J.Fan, D.M.Mills, A.C.Arvanites, H.Orgueira, M.A.Ashwell, G.Carmel, Y.Xiang, and D.T.Moir (2004).
Identification and characterization of inhibitors of bacterial enoyl-acyl carrier protein reductase.
  Antimicrob Agents Chemother, 48, 1541-1547.  
  15043388 R.J.Heath, and C.O.Rock (2004).
Fatty acid biosynthesis as a target for novel antibacterials.
  Curr Opin Investig Drugs, 5, 146-153.  
14987762 Y.Ji, D.Yin, B.Fox, D.J.Holmes, D.Payne, and M.Rosenberg (2004).
Validation of antibacterial mechanism of action using regulated antisense RNA expression in Staphylococcus aureus.
  FEMS Microbiol Lett, 231, 177-184.  
15726819 Y.M.Zhang, Y.J.Lu, and C.O.Rock (2004).
The reductase steps of the type II fatty acid synthase as antimicrobial targets.
  Lipids, 39, 1055-1060.  
12826118 A.Golebiowski, S.R.Klopfenstein, and D.E.Portlock (2003).
Lead compounds discovered from libraries: part 2.
  Curr Opin Chem Biol, 7, 308-325.  
12606558 M.R.Kuo, H.R.Morbidoni, D.Alland, S.F.Sneddon, B.B.Gourlie, M.M.Staveski, M.Leonard, J.S.Gregory, A.D.Janjigian, C.Yee, J.M.Musser, B.Kreiswirth, H.Iwamoto, R.Perozzo, W.R.Jacobs, J.C.Sacchettini, and D.A.Fidock (2003).
Targeting tuberculosis and malaria through inhibition of Enoyl reductase: compound activity and structural data.
  J Biol Chem, 278, 20851-20859.
PDB codes: 1p44 1p45
12000610 D.McDevitt, D.J.Payne, D.J.Holmes, and M.Rosenberg (2002).
Novel targets for the future development of antibacterial agents.
  J Appl Microbiol, 92, 28S-34S.  
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.