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

doi:10.1074/jbc.M113.529164

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

Pharmacology

Research output: Contribution to journal › Article › peer-review

126 Scopus citations

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 language	English (US)
Pages (from-to)	12300-12312
Number of pages	13
Journal	Journal of Biological Chemistry
Volume	289
Issue number	18
DOIs	https://doi.org/10.1074/jbc.M113.529164
State	Published - 2014

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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.",

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AU - Mustaev, Arkady

AU - Malik, Muhammad

AU - Zhao, Xilin

AU - Kurepina, Natalia

AU - Luan, Gan

AU - Oppegard, Lisa M.

AU - Hiasa, Hiroshi

AU - Marks, Kevin R.

AU - Kerns, Robert J.

AU - Berger, James M.

AU - Drlica, Karl

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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Fluoroquinolone-gyrase-DNA complexes two modes of drug binding

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