Crystallographic analysis of triclosan bound to enoyl reductase

J Mol Biol. 1999 Nov 26;294(2):527-35. doi: 10.1006/jmbi.1999.3240.


Molecular genetic studies with strains of Escherichia coli resistant to triclosan, an ingredient of many anti-bacterial household goods, have suggested that this compound works by acting as an inhibitor of enoyl reductase (ENR) and thereby blocking lipid biosynthesis. We present structural analyses correlated with inhibition data, on the complexes of E. coli and Brassica napus ENR with triclosan and NAD(+) which reveal how triclosan acts as a site-directed, picomolar inhibitor of the enzyme by mimicking its natural substrate. Elements of both the protein and the nucleotide cofactor play important roles in triclosan recognition, providing an explanation for the factors controlling its tight binding to the enzyme and for the emergence of triclosan resistance.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents, Local / chemistry*
  • Anti-Infective Agents, Local / metabolism*
  • Binding Sites
  • Boron Compounds / metabolism
  • Brassica / chemistry
  • Crystallography, X-Ray
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)
  • Enzyme Inhibitors / metabolism
  • Escherichia coli / enzymology
  • Models, Molecular
  • Oxidoreductases / antagonists & inhibitors
  • Oxidoreductases / chemistry*
  • Oxidoreductases / metabolism*
  • Plant Proteins / chemistry
  • Protein Conformation
  • Triclosan / chemistry*
  • Triclosan / metabolism*


  • Anti-Infective Agents, Local
  • Boron Compounds
  • Enzyme Inhibitors
  • Plant Proteins
  • Triclosan
  • 1,2-dihydro-1-hydroxy-6-methyl-2-(propanesulfonyl)-thieno(3,2D)(1,2,3)-diazaborine
  • Oxidoreductases
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)

Associated data

  • PDB/1D70
  • PDB/1D8A
  • PDB/1QG6