 |
PDBsum entry 3vod
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transcription
|
PDB id
|
|
|
|
3vod
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
The multiple antibiotic resistance regulator marr is a copper sensor in escherichia coli.
|
|
|
Authors
|
|
Z.Hao,
H.Lou,
R.Zhu,
J.Zhu,
D.Zhang,
B.S.Zhao,
S.Zeng,
X.Chen,
J.Chan,
C.He,
P.R.Chen.
|
|
|
Ref.
|
|
Nat Chem Biol, 2014,
10,
21-28.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
