DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs

Zhou Yin, Yao Wang, Louise R. Whittell, Slobodan Jergic, Michael Liu, Elizabeth Harry, Nicholas E. Dixon, Michael J. Kelso, Jennifer L. Beck, Aaron J. Oakley

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III β subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase α subunit with the sliding clamp is demonstrated using an in vitro DNA replication assay. NSAIDs thus present promising lead scaffolds for novel antibacterial agents targeting the sliding clamp.

Original languageEnglish (US)
Pages (from-to)481-487
Number of pages7
JournalChemistry and Biology
Volume21
Issue number4
DOIs
StatePublished - Apr 24 2014
Externally publishedYes

Fingerprint

DNA Replication
Clamping devices
Anti-Inflammatory Agents
DNA
Pharmaceutical Preparations
DNA Polymerase III
Loaders
Scaffolds
DNA Repair
Escherichia coli
Assays
Repair
Crystal structure
Binding Sites
Anti-Bacterial Agents
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Molecular Biology
  • Clinical Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Medicine(all)

Cite this

Yin, Z., Wang, Y., Whittell, L. R., Jergic, S., Liu, M., Harry, E., ... Oakley, A. J. (2014). DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs. Chemistry and Biology, 21(4), 481-487. https://doi.org/10.1016/j.chembiol.2014.02.009

DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs. / Yin, Zhou; Wang, Yao; Whittell, Louise R.; Jergic, Slobodan; Liu, Michael; Harry, Elizabeth; Dixon, Nicholas E.; Kelso, Michael J.; Beck, Jennifer L.; Oakley, Aaron J.

In: Chemistry and Biology, Vol. 21, No. 4, 24.04.2014, p. 481-487.

Research output: Contribution to journalArticle

Yin, Z, Wang, Y, Whittell, LR, Jergic, S, Liu, M, Harry, E, Dixon, NE, Kelso, MJ, Beck, JL & Oakley, AJ 2014, 'DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs', Chemistry and Biology, vol. 21, no. 4, pp. 481-487. https://doi.org/10.1016/j.chembiol.2014.02.009
Yin, Zhou ; Wang, Yao ; Whittell, Louise R. ; Jergic, Slobodan ; Liu, Michael ; Harry, Elizabeth ; Dixon, Nicholas E. ; Kelso, Michael J. ; Beck, Jennifer L. ; Oakley, Aaron J. / DNA replication is the target for the antibacterial effects of nonsteroidal anti-inflammatory drugs. In: Chemistry and Biology. 2014 ; Vol. 21, No. 4. pp. 481-487.
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