Fluoroquinolone-gyrase-DNA complexes two modes of drug binding

Arkady Mustaev, Muhammad Malik, Xilin Zhao, Natalia Kurepina, Gan Luan, Lisa M. Oppegard, Hiroshi Hiasa, Kevin R. Marks, Robert J. Kerns, James M Berger, Karl Drlica

Research output: Contribution to journalArticle

Abstract

Background: X-ray crystal structures of fluoroquinolone-gyrase-DNA complexes reveal a single drug-binding mode. Results: A ciprofloxacin derivative with a chloroacetyl moiety at the C-7 end cross-linked with cysteine substitutions in both GyrA and GyrB that were 17 A apart. Conclusion: Cleaved complexes containing gyrase have two fluoroquinolone-binding modes. Significance: The additional drug-binding mode provides new ways to investigate inhibitor-topoisomerase interactions.

Original languageEnglish (US)
Pages (from-to)12300-12312
Number of pages13
JournalJournal of Biological Chemistry
Volume289
Issue number18
DOIs
StatePublished - 2014

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DNA Gyrase
Fluoroquinolones
Topoisomerase Inhibitors
Ciprofloxacin
Pharmaceutical Preparations
Cysteine
Substitution reactions
Crystal structure
X-Rays
Derivatives
X rays

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Mustaev, A., Malik, M., Zhao, X., Kurepina, N., Luan, G., Oppegard, L. M., ... Drlica, K. (2014). Fluoroquinolone-gyrase-DNA complexes two modes of drug binding. Journal of Biological Chemistry, 289(18), 12300-12312. https://doi.org/10.1074/jbc.M113.529164

Fluoroquinolone-gyrase-DNA complexes two modes of drug binding. / Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M.; Hiasa, Hiroshi; Marks, Kevin R.; Kerns, Robert J.; Berger, James M; Drlica, Karl.

In: Journal of Biological Chemistry, Vol. 289, No. 18, 2014, p. 12300-12312.

Research output: Contribution to journalArticle

Mustaev, A, Malik, M, Zhao, X, Kurepina, N, Luan, G, Oppegard, LM, Hiasa, H, Marks, KR, Kerns, RJ, Berger, JM & Drlica, K 2014, 'Fluoroquinolone-gyrase-DNA complexes two modes of drug binding', Journal of Biological Chemistry, vol. 289, no. 18, pp. 12300-12312. https://doi.org/10.1074/jbc.M113.529164
Mustaev A, Malik M, Zhao X, Kurepina N, Luan G, Oppegard LM et al. Fluoroquinolone-gyrase-DNA complexes two modes of drug binding. Journal of Biological Chemistry. 2014;289(18):12300-12312. https://doi.org/10.1074/jbc.M113.529164
Mustaev, Arkady ; Malik, Muhammad ; Zhao, Xilin ; Kurepina, Natalia ; Luan, Gan ; Oppegard, Lisa M. ; Hiasa, Hiroshi ; Marks, Kevin R. ; Kerns, Robert J. ; Berger, James M ; Drlica, Karl. / Fluoroquinolone-gyrase-DNA complexes two modes of drug binding. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 18. pp. 12300-12312.
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