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PDBsum entry 2hqf

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protein links
Membrane protein PDB id
2hqf
Jmol
Contents
Protein chain
1016 a.a. *
* Residue conservation analysis
PDB id:
2hqf
Name: Membrane protein
Title: Conformation of the acrb multidrug efflux pump in mutants of putative proton relay pathway
Structure: Acriflavine resistance protein b. Chain: a. Synonym: acrb membrane transporter. Engineered: yes. Mutation: yes
Source: Escherichia coli k12. Organism_taxid: 83333. Strain: k-12. Gene: acrb, acre, b0462. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
3.38Å     R-factor:   0.252     R-free:   0.280
Authors: C.-C.Su,M.Li,R.Gu,Y.Takatsuka,G.Mcdermott,H.Nikaido,E.W.Yu
Key ref: 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: 17015668
Date:
18-Jul-06     Release date:   17-Apr-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P31224  (ACRB_ECOLI) -  Multidrug efflux pump subunit AcrB
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1049 a.a.
1016 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   4 terms 
  Biological process     transport   4 terms 
  Biochemical function     transporter activity     4 terms  

 

 
J Bacteriol 188:7290-7296 (2006)
PubMed id: 17015668  
 
 
Conformation of the AcrB multidrug efflux pump in mutants of the putative proton relay pathway.
C.C.Su, M.Li, R.Gu, Y.Takatsuka, G.McDermott, H.Nikaido, E.W.Yu.
 
  ABSTRACT  
 
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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20981744 C.C.Su, F.Long, and E.W.Yu (2011).
The Cus efflux system removes toxic ions via a methionine shuttle.
  Protein Sci, 20, 6.  
21350490 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.
  Nature, 470, 558-562.
PDB code: 3ne5
20583998 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.
  Biochem J, 430, 355-364.  
20804453 F.Husain, and H.Nikaido (2010).
Substrate path in the AcrB multidrug efflux pump of Escherichia coli.
  Mol Microbiol, 78, 320-330.  
20865003 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.
  Nature, 467, 484-488.
PDB codes: 3k07 3kso 3kss
20399187 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.
  Structure, 18, 507-517.
PDB code: 3d5k
20038594 H.S.Kim, D.Nagore, and H.Nikaido (2010).
Multidrug efflux pump MdtBC of Escherichia coli is active only as a B2C heterotrimer.
  J Bacteriol, 192, 1377-1386.  
20212112 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.
  Proc Natl Acad Sci U S A, 107, 6559-6565.  
19593437 A.Deniaud, A.Goulielmakis, J.Covès, and E.Pebay-Peyroula (2009).
Differences between CusA and AcrB crystallisation highlighted by protein flexibility.
  PLoS One, 4, e6214.  
19033246 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).
  J Antimicrob Chemother, 63, 290-294.  
19136595 H.I.Zgurskaya (2009).
Covalently linked AcrB giant offers a new powerful tool for mechanistic analysis of multidrug efflux in bacteria.
  J Bacteriol, 191, 1727-1728.  
19722844 H.I.Zgurskaya (2009).
Multicomponent drug efflux complexes: architecture and mechanism of assembly.
  Future Microbiol, 4, 919-932.  
19026770 H.Nikaido, and Y.Takatsuka (2009).
Mechanisms of RND multidrug efflux pumps.
  Biochim Biophys Acta, 1794, 769-781.  
19231985 H.Nikaido (2009).
Multidrug resistance in bacteria.
  Annu Rev Biochem, 78, 119-146.  
19289182 R.Misra, and V.N.Bavro (2009).
Assembly and transport mechanism of tripartite drug efflux systems.
  Biochim Biophys Acta, 1794, 817-825.  
19453279 T.Eicher, L.Brandstätter, and K.M.Pos (2009).
Structural and functional aspects of the multidrug efflux pump AcrB.
  Biol Chem, 390, 693-699.  
19678712 X.Z.Li, and H.Nikaido (2009).
Efflux-mediated drug resistance in bacteria: an update.
  Drugs, 69, 1555-1623.  
19060146 Y.Takatsuka, and H.Nikaido (2009).
Covalently linked trimer of the AcrB multidrug efflux pump provides support for the functional rotating mechanism.
  J Bacteriol, 191, 1729-1737.  
17910961 C.C.Su, H.Nikaido, and E.W.Yu (2007).
Ligand-transporter interaction in the AcrB multidrug efflux pump determined by fluorescence polarization assay.
  FEBS Lett, 581, 4972-4976.  
17159924 O.Lomovskaya, H.I.Zgurskaya, M.Totrov, and W.J.Watkins (2007).
Waltzing transporters and 'the dance macabre' between humans and bacteria.
  Nat Rev Drug Discov, 6, 56-65.  
18073115 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.
  Structure, 15, 1663-1673.
PDB code: 2rdd
17905989 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.
  J Bacteriol, 189, 8677-8684.  
17015667 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.
  J Bacteriol, 188, 7284-7289.  
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.