 |
PDBsum entry 3f8b
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transcription regulator
|
PDB id
|
|
|
|
3f8b
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
| |
|
|
Embo J
28:156-166
(2009)
|
|
PubMed id:
|
|
|
|
|
|
| |
|
Structure of the transcriptional regulator LmrR and its mechanism of multidrug recognition.
|
|
P.K.Madoori,
H.Agustiandari,
A.J.Driessen,
A.M.Thunnissen.
|
|
|
|
|
| |
ABSTRACT
|
|
|
|
| |
|
|
LmrR is a PadR-related transcriptional repressor that regulates the production
of LmrCD, a major multidrug ABC transporter in Lactococcus lactis.
Transcriptional regulation is presumed to follow a drug-sensitive induction
mechanism involving the direct binding of transporter ligands to LmrR. Here, we
present crystal structures of LmrR in an apo state and in two drug-bound states
complexed with Hoechst 33342 and daunomycin. LmrR shows a common topology
containing a typical beta-winged helix-turn-helix domain with an additional
C-terminal helix involved in dimerization. Its dimeric organization is highly
unusual with a flat-shaped hydrophobic pore at the dimer centre serving as a
multidrug-binding site. The drugs bind in a similar manner with their aromatic
rings sandwiched in between the indole groups of two dimer-related tryptophan
residues. Multidrug recognition is facilitated by conformational plasticity and
the absence of drug-specific hydrogen bonds. Combined analyses using
site-directed mutagenesis, fluorescence-based drug binding and protein-DNA gel
shift assays reveal an allosteric coupling between the multidrug- and
DNA-binding sites of LmrR that most likely has a function in the induction
mechanism.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
 |
 |
|
Literature references that cite this PDB file's key reference
|
|
|
| |
PubMed id
|
|
Reference
|
|
|
|
|
|
H.Agustiandari,
E.Peeters,
J.G.de Wit,
D.Charlier,
and
A.J.Driessen
(2011).
LmrR-mediated gene regulation of multidrug resistance in Lactococcus lactis.
|
| |
Microbiology,
157,
1519-1530.
|
|
|
|
|
|
|
K.M.Peters,
B.E.Brooks,
M.A.Schumacher,
R.A.Skurray,
R.G.Brennan,
and
M.H.Brown
(2011).
A single acidic residue can guide binding site selection but does not govern QacR cationic-drug affinity.
|
| |
PLoS One,
6,
e15974.
|
|
|
PDB code:
|
|
|
|
|
|
|
|
C.Andrésen,
S.Jalal,
D.Aili,
Y.Wang,
S.Islam,
A.Jarl,
B.Liedberg,
B.Wretlind,
L.G.Mårtensson,
and
M.Sunnerhagen
(2010).
Critical biophysical properties in the Pseudomonas aeruginosa efflux gene regulator MexR are targeted by mutations conferring multidrug resistance.
|
| |
Protein Sci,
19,
680-692.
|
|
|
|
|
|
|
G.Zhang,
Y.Tian,
K.Hu,
C.Feng,
and
H.Tan
(2010).
SCO3900, co-transcripted with three downstream genes, is involved in the differentiation of Streptomyces coelicolor.
|
| |
Curr Microbiol,
60,
268-273.
|
|
|
|
|
|
|
H.Wade
(2010).
MD recognition by MDR gene regulators.
|
| |
Curr Opin Struct Biol,
20,
489-496.
|
|
|
|
|
|
|
J.Gury,
H.Seraut,
N.P.Tran,
L.Barthelmebs,
S.Weidmann,
P.Gervais,
and
J.F.Cavin
(2009).
Inactivation of PadR, the repressor of the phenolic acid stress response, by molecular interaction with Usp1, a universal stress protein from Lactobacillus plantarum, in Escherichia coli.
|
| |
Appl Environ Microbiol,
75,
5273-5283.
|
|
|
|
|
|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
|
|
|
Links
