Research Abstract



The crystal structure of multidrug-resistance regulator RamR with multiple drugs

2013年6月26日 Nature Communications 4 : 2078 doi: 10.1038/ncomms3078


山崎 優1, 2, 二階堂 英司1, 2, 中島 良介3, 櫻井 啓介3, 藤原 大佑4, 藤井 郁雄4 & 西野 邦彦1

  1. 大阪大学 産業科学研究所 特別プロジェクト研究部門 感染制御学研究分野
  2. 大阪大学大学院 薬学研究科
  3. 大阪大学 産業科学研究所 特別プロジェクト研究部門 生体防御学研究分野
  4. 大阪府立大学大学院 理学系研究科 生物科学専攻
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.