Author
Listed:
- Suguru Yamasaki
(Laboratory of Microbiology and Infectious Diseases, Institute of Scientific and Industrial Research, Osaka University
Graduate School of Pharmaceutical Sciences, Osaka University)
- Eiji Nikaido
(Laboratory of Microbiology and Infectious Diseases, Institute of Scientific and Industrial Research, Osaka University
Graduate School of Pharmaceutical Sciences, Osaka University)
- Ryosuke Nakashima
(Laboratory of Cell Membrane Structure Biology, Institute of Scientific and Industrial Research, Osaka University)
- Keisuke Sakurai
(Laboratory of Cell Membrane Structure Biology, Institute of Scientific and Industrial Research, Osaka University)
- Daisuke Fujiwara
(Graduate School of Science, Osaka Prefecture University)
- Ikuo Fujii
(Graduate School of Science, Osaka Prefecture University)
- Kunihiko Nishino
(Laboratory of Microbiology and Infectious Diseases, Institute of Scientific and Industrial Research, Osaka University)
Abstract
RamR is a transcriptional repressor of the gene-encoding RamA protein, which controls the expression of the multidrug efflux system genes acrAB-tolC. RamR is an important multidrug-resistance factor, however, its structure and the identity of the molecules to which it responds have been unknown. Here, we report the crystal structure of RamR in complex with multiple drugs, including berberine, crystal violet, dequalinium, ethidium bromide and rhodamine 6G. All compounds are found to interact with Phe155 of RamR, and each compound is surrounded by different amino acid residues. Binding of these compounds to RamR reduces its DNA-binding affinity, which results in the increased expression of ramA. Our results reveal significant flexibility in the substrate-recognition region of RamR, which regulates the bacterial efflux participating in multidrug resistance.
Suggested Citation
Suguru Yamasaki & Eiji Nikaido & Ryosuke Nakashima & Keisuke Sakurai & Daisuke Fujiwara & Ikuo Fujii & Kunihiko Nishino, 2013.
"The crystal structure of multidrug-resistance regulator RamR with multiple drugs,"
Nature Communications, Nature, vol. 4(1), pages 1-7, October.
Handle:
RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3078
DOI: 10.1038/ncomms3078
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