4JBA

Crystal Structure of the Oxidized Form of MarR from E.coli

Summary for 4JBA

• Entry DOI: 10.2210/pdb4jba/pdb
• Descriptor: Multiple antibiotic resistance protein MarR (2 entities in total)
• Functional Keywords: disulfide bonds, transcription regulator, dna, transcription regulation
• Biological source: Escherichia coli
• Total number of polymer chains: 2
• Total formula weight: 32013.39

Authors

Lou, H.,Zhu, R.,Hao, Z. (deposition date: 2013-02-19, release date: 2013-10-16, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)