3VOD

Crystal Structure of mutant MarR C80S from E.coli

3VOD の概要

• エントリーDOI: 10.2210/pdb3vod/pdb
• 関連するPDBエントリー: 3VOE
• 分子名称: Multiple antibiotic resistance protein marR (1 entity in total)
• 機能のキーワード: winged helix-turn-helix dna binding motif, transcription
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 32141.91

構造登録者

Lou, H.,Zhu, R.,Hao, Z. (登録日: 2012-01-21, 公開日: 2013-03-06, 最終更新日: 2024-03-20)

主引用文献

Hao, Z.,Lou, H.,Zhu, R.,Zhu, J.,Zhang, D.,Zhao, B.S.,Zeng, S.,Chen, X.,Chan, J.,He, C.,Chen, P.R.
The multiple antibiotic resistance regulator MarR is a copper sensor in Escherichia coli.
Nat.Chem.Biol., 10:21-28, 2014

PubMed Abstract: The widely conserved multiple antibiotic resistance regulator (MarR) family of transcription factors modulates bacterial detoxification in response to diverse antibiotics, toxic chemicals or both. The natural inducer for Escherichia coli MarR, the prototypical transcription repressor within this family, remains unknown. Here we show that copper signaling potentiates MarR derepression in E. coli. Copper(II) oxidizes a cysteine residue (Cys80) on MarR to generate disulfide bonds between two MarR dimers, thereby inducing tetramer formation and the dissociation of MarR from its cognate promoter DNA. We further discovered that salicylate, a putative MarR inducer, and the clinically important bactericidal antibiotics norfloxacin and ampicillin all stimulate intracellular copper elevation, most likely through oxidative impairment of copper-dependent envelope proteins, including NADH dehydrogenase-2. This membrane-associated copper oxidation and liberation process derepresses MarR, causing increased bacterial antibiotic resistance. Our study reveals that this bacterial transcription regulator senses copper(II) as a natural signal to cope with stress caused by antibiotics or the environment.

PubMed: 24185215
DOI: 10.1038/nchembio.1380

実験手法

X-RAY DIFFRACTION (2.6 Å)