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PDBsum entry 2hqc
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Membrane protein
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PDB id
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2hqc
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Contents |
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* Residue conservation analysis
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PDB id:
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Membrane protein
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Title:
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Conformation of the acrb multidrug efflux pump in mutants of the putative proton relay pathway
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Structure:
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Acriflavine resistance protein b. Chain: a. Synonym: acrb membrane transporter. Engineered: yes. Mutation: yes
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Source:
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Escherichia coli k12. Organism_taxid: 83333. Strain: k-12. Gene: acrb, acre, b0462. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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3.56Å
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R-factor:
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0.272
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R-free:
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0.294
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Authors:
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C.-C.Su,M.Li,R.Gu,Y.Takatsuka,G.Mcdermott,H.Nikaido,E.W.Yu
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Key ref:
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C.C.Su
et al.
(2006).
Conformation of the AcrB multidrug efflux pump in mutants of the putative proton relay pathway.
J Bacteriol,
188,
7290-7296.
PubMed id:
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Date:
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18-Jul-06
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Release date:
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17-Apr-07
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PROCHECK
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Headers
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References
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P31224
(ACRB_ECOLI) -
Multidrug efflux pump subunit AcrB from Escherichia coli (strain K12)
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Seq:
Struc:
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1049 a.a.
1016 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 1 residue position (black
cross)
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J Bacteriol
188:7290-7296
(2006)
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PubMed id:
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Conformation of the AcrB multidrug efflux pump in mutants of the putative proton relay pathway.
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C.C.Su,
M.Li,
R.Gu,
Y.Takatsuka,
G.McDermott,
H.Nikaido,
E.W.Yu.
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ABSTRACT
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We previously reported the X-ray structures of wild-type Escherichia coli AcrB,
a proton motive force-dependent multidrug efflux pump, and its N109A mutant.
These structures presumably reflect the resting state of AcrB, which can bind
drugs. After ligand binding, a proton may bind to an acidic residue(s) in the
transmembrane domain, i.e., Asp407 or Asp408, within the putative network of
electrostatically interacting residues, which also include Lys940 and Thr978,
and this may initiate a series of conformational changes that result in drug
expulsion. Herein we report the X-ray structures of four AcrB mutants, the
D407A, D408A, K940A, and T978A mutants, in which the structure of this tight
electrostatic network is expected to become disrupted. These mutant proteins
revealed remarkably similar conformations, which show striking differences from
the previously known conformations of the wild-type protein. For example, the
loop containing Phe386 and Phe388, which play a major role in the initial
binding of substrates in the central cavity, becomes prominently extended into
the center of the cavity, such that binding of large substrate molecules may
become difficult. We believe that this new conformation may mimic, at least
partially, one of the transient conformations of the transporter during the
transport cycle.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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C.C.Su,
F.Long,
and
E.W.Yu
(2011).
The Cus efflux system removes toxic ions via a methionine shuttle.
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Protein Sci,
20,
6.
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C.C.Su,
F.Long,
M.T.Zimmermann,
K.R.Rajashankar,
R.L.Jernigan,
and
E.W.Yu
(2011).
Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli.
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Nature,
470,
558-562.
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PDB code:
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A.Welch,
C.U.Awah,
S.Jing,
H.W.van Veen,
and
H.Venter
(2010).
Promiscuous partnering and independent activity of MexB, the multidrug transporter protein from Pseudomonas aeruginosa.
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Biochem J,
430,
355-364.
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F.Husain,
and
H.Nikaido
(2010).
Substrate path in the AcrB multidrug efflux pump of Escherichia coli.
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Mol Microbiol,
78,
320-330.
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F.Long,
C.C.Su,
M.T.Zimmermann,
S.E.Boyken,
K.R.Rajashankar,
R.L.Jernigan,
and
E.W.Yu
(2010).
Crystal structures of the CusA efflux pump suggest methionine-mediated metal transport.
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Nature,
467,
484-488.
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PDB codes:
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G.Phan,
H.Benabdelhak,
M.B.Lascombe,
P.Benas,
S.Rety,
M.Picard,
A.Ducruix,
C.Etchebest,
and
I.Broutin
(2010).
Structural and dynamical insights into the opening mechanism of P. aeruginosa OprM channel.
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Structure,
18,
507-517.
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PDB code:
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H.S.Kim,
D.Nagore,
and
H.Nikaido
(2010).
Multidrug efflux pump MdtBC of Escherichia coli is active only as a B2C heterotrimer.
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J Bacteriol,
192,
1377-1386.
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Y.Takatsuka,
C.Chen,
and
H.Nikaido
(2010).
Mechanism of recognition of compounds of diverse structures by the multidrug efflux pump AcrB of Escherichia coli.
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Proc Natl Acad Sci U S A,
107,
6559-6565.
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A.Deniaud,
A.Goulielmakis,
J.Covès,
and
E.Pebay-Peyroula
(2009).
Differences between CusA and AcrB crystallisation highlighted by protein flexibility.
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PLoS One,
4,
e6214.
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A.Preisler,
and
P.Heisig
(2009).
The role of intra- and extragenic compensatory mutations in the suppression of fluoroquinolone resistance in a Salmonella Typhimurium gyrA mutant (D87G).
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J Antimicrob Chemother,
63,
290-294.
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H.I.Zgurskaya
(2009).
Covalently linked AcrB giant offers a new powerful tool for mechanistic analysis of multidrug efflux in bacteria.
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J Bacteriol,
191,
1727-1728.
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H.I.Zgurskaya
(2009).
Multicomponent drug efflux complexes: architecture and mechanism of assembly.
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Future Microbiol,
4,
919-932.
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H.Nikaido,
and
Y.Takatsuka
(2009).
Mechanisms of RND multidrug efflux pumps.
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Biochim Biophys Acta,
1794,
769-781.
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H.Nikaido
(2009).
Multidrug resistance in bacteria.
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Annu Rev Biochem,
78,
119-146.
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R.Misra,
and
V.N.Bavro
(2009).
Assembly and transport mechanism of tripartite drug efflux systems.
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Biochim Biophys Acta,
1794,
817-825.
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T.Eicher,
L.Brandstätter,
and
K.M.Pos
(2009).
Structural and functional aspects of the multidrug efflux pump AcrB.
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Biol Chem,
390,
693-699.
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X.Z.Li,
and
H.Nikaido
(2009).
Efflux-mediated drug resistance in bacteria: an update.
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Drugs,
69,
1555-1623.
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Y.Takatsuka,
and
H.Nikaido
(2009).
Covalently linked trimer of the AcrB multidrug efflux pump provides support for the functional rotating mechanism.
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J Bacteriol,
191,
1729-1737.
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C.C.Su,
H.Nikaido,
and
E.W.Yu
(2007).
Ligand-transporter interaction in the AcrB multidrug efflux pump determined by fluorescence polarization assay.
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FEBS Lett,
581,
4972-4976.
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O.Lomovskaya,
H.I.Zgurskaya,
M.Totrov,
and
W.J.Watkins
(2007).
Waltzing transporters and 'the dance macabre' between humans and bacteria.
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Nat Rev Drug Discov,
6,
56-65.
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S.Törnroth-Horsefield,
P.Gourdon,
R.Horsefield,
L.Brive,
N.Yamamoto,
H.Mori,
A.Snijder,
and
R.Neutze
(2007).
Crystal structure of AcrB in complex with a single transmembrane subunit reveals another twist.
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Structure,
15,
1663-1673.
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PDB code:
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Y.Takatsuka,
and
H.Nikaido
(2007).
Site-directed disulfide cross-linking shows that cleft flexibility in the periplasmic domain is needed for the multidrug efflux pump AcrB of Escherichia coli.
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J Bacteriol,
189,
8677-8684.
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Y.Takatsuka,
and
H.Nikaido
(2006).
Threonine-978 in the transmembrane segment of the multidrug efflux pump AcrB of Escherichia coli is crucial for drug transport as a probable component of the proton relay network.
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J Bacteriol,
188,
7284-7289.
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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.
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Links
