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PDBsum entry 1v35
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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1v35

 

 

 

 

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Contents
Protein chains
287 a.a. *
Ligands
NAI ×2
Waters ×178
* Residue conservation analysis
PDB id:
1v35
Name: Oxidoreductase
Title: Crystal structure of eoyl-acp reductase with nadh
Structure: Enoyl-acp reductase. Chain: a, b. Fragment: residues 96-424. Engineered: yes
Source: Plasmodium falciparum. Malaria parasite p. Falciparum. Organism_taxid: 5833. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Tetramer (from PDB file)
Resolution:
2.50Å     R-factor:   0.165     R-free:   0.202
Authors: P.L.Swarnamukhi,M.Kapoor,N.Surolia,A.Surolia,K.Suguna
Key ref:
L.S.Pidugu et al. (2004). Structural basis for the variation in triclosan affinity to enoyl reductases. J Mol Biol, 343, 147-155. PubMed id: 15381426 DOI: 10.1016/j.jmb.2004.08.033
Date:
28-Oct-03     Release date:   28-Sep-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9BJJ9  (Q9BJJ9_PLAFA) -  Enoyl-ACP reductase (Fragment) from Plasmodium falciparum
Seq:
Struc: 		432 a.a.
287 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: a 2,3-saturated acyl-[ACP] + NAD+ = a (2E)-enoyl-[ACP] + NADH + H+
2,3-saturated acyl-[ACP]
 +
NAD(+)
Bound ligand (Het Group name = NAI)
corresponds exactly 		= (2E)-enoyl-[ACP]
 + NADH
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
DOI no: 10.1016/j.jmb.2004.08.033 J Mol Biol 343:147-155 (2004)
PubMed id: 15381426  
 
 
Structural basis for the variation in triclosan affinity to enoyl reductases.
L.S.Pidugu, M.Kapoor, N.Surolia, A.Surolia, K.Suguna.
 
  ABSTRACT  
 
Bacteria synthesize fatty acids in a dissociated type pathway different from that in humans. Enoyl acyl carrier protein reductase, which catalyzes the final step of fatty acid elongation, has been validated as a potential anti-microbial drug target. Triclosan is known to inhibit this enzyme effectively. Precise characterization of the mode of triclosan binding is required to develop highly specific inhibitors. With this in view, interactions between triclosan, the cofactor NADH/NAD+ and the enzyme from five different species, one plant and four of microbial origin, have been examined in the available crystal structures. A comparison of these structures shows major structural differences at the substrate/inhibitor/cofactor-binding loop. The analysis reveals that the conformation of this flexible loop and the binding affinities of triclosan to each of these enzymes are strongly correlated.
 
  Selected figure(s)  
 
Figure 9.
Figure 9. Hydrogen bonds between the adenine ring of NAD C and the protein in pfENR. 		Figure 10.
Figure 10. 2FoKFc electron den- sity map contoured at 1.5s for cofactor NAD C and inhibitor tri- closan. The Figures have been generated using the program BOB- SCRIPT 41 and rendered using RASTER3D. 40
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 343, 147-155) copyright 2004.  
  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.  
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.  
20055482 H.Lu, and P.J.Tonge (2010).
Mechanism and inhibition of the FabV enoyl-ACP reductase from Burkholderia mallei.
  Biochemistry, 49, 1281-1289.  
21035728 W.Mattheus, J.Masschelein, L.J.Gao, P.Herdewijn, B.Landuyt, G.Volckaert, and R.Lavigne (2010).
The kalimantacin/batumin biosynthesis operon encodes a self-resistance isoform of the FabI bacterial target.
  Chem Biol, 17, 1067-1071.  
19701949 A.P.Singh, N.Surolia, and A.Surolia (2009).
Triclosan inhibit the growth of the late liver-stage of Plasmodium.
  IUBMB Life, 61, 923-928.  
19424997 K.Gademann, and J.Kobylinska (2009).
Antimalarial natural products of marine and freshwater origin.
  Chem Rec, 9, 187-198.  
19859979 N.Kapoor, T.Banerjee, P.Babu, K.Maity, N.Surolia, and A.Surolia (2009).
Design, development, synthesis, and docking analysis of 2'-substituted triclosan analogs as inhibitors for Plasmodium falciparum Enoyl-ACP reductase.
  IUBMB Life, 61, 1083-1091.  
19527659 R.Potestio, F.Pontiggia, and C.Micheletti (2009).
Coarse-grained description of protein internal dynamics: an optimal strategy for decomposing proteins in rigid subunits.
  Biophys J, 96, 4993-5002.  
19347595 V.A.Morde, M.S.Shaikh, R.R.Pissurlenkar, and E.C.Coutinho (2009).
Molecular modeling studies, synthesis, and biological evaluation of Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR) inhibitors.
  Mol Divers, 13, 501-517.  
18369194 A.Zen, V.Carnevale, A.M.Lesk, and C.Micheletti (2008).
Correspondences between low-energy modes in enzymes: dynamics-based alignment of enzymatic functional families.
  Protein Sci, 17, 918-929.  
18663709 S.K.Tipparaju, D.C.Mulhearn, G.M.Klein, Y.Chen, S.Tapadar, M.H.Bishop, S.Yang, J.Chen, M.Ghassemi, B.D.Santarsiero, J.L.Cook, M.Johlfs, A.D.Mesecar, M.E.Johnson, and A.P.Kozikowski (2008).
Design and synthesis of aryl ether inhibitors of the Bacillus anthracis enoyl-ACP reductase.
  ChemMedChem, 3, 1250-1268.
PDB code: 2qio
17879346 H.H.Lee, J.Moon, and S.W.Suh (2007).
Crystal structure of the Helicobacter pylori enoyl-acyl carrier protein reductase in complex with hydroxydiphenyl ether compounds, triclosan and diclosan.
  Proteins, 69, 691-694.
PDB codes: 1jvf 1jw7 2pd3 2pd4
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
  16754986 J.Saito, M.Yamada, T.Watanabe, H.Kitagawa, and Y.Takeuchi (2006).
Crystallization and preliminary X-ray analysis of enoyl-acyl carrier protein reductase (FabK) from Streptococcus pneumoniae.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 576-578.  
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.

 

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