Crystallographic analysis of triclosan bound to enoyl reductase

Anna Roujeinikova, Colin W. Levy, Siân Rowsell, Svetlana Sedelnikova, Patrick J. Baker, Claire A. Minshull, Anil Mistry, Jeremey G. Colls, Roger Camble, Antoine R. Stuitje, Antoni R. Slabas, John B. Rafferty, Richard A. Pauptit, Russell Viner, David W. Rice

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Abstract

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.

Original languageEnglish
Pages (from-to)527-535
Number of pages9
JournalJournal of Molecular Biology
Volume294
Issue number2
DOIs
Publication statusPublished - 26 Nov 1999
Externally publishedYes

Keywords

  • Crystal structure
  • Enoyl reductase
  • Inhibitor binding
  • Resistance
  • Triclosan

Cite this

Roujeinikova, A., Levy, C. W., Rowsell, S., Sedelnikova, S., Baker, P. J., Minshull, C. A., Mistry, A., Colls, J. G., Camble, R., Stuitje, A. R., Slabas, A. R., Rafferty, J. B., Pauptit, R. A., Viner, R., & Rice, D. W. (1999). Crystallographic analysis of triclosan bound to enoyl reductase. Journal of Molecular Biology, 294(2), 527-535. https://doi.org/10.1006/jmbi.1999.3240