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PDBsum entry 1s7b

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protein Protein-protein interface(s) links
Transport protein PDB id
1s7b
Jmol
Contents
Protein chains
(+ 2 more) 106 a.a.
Obsolete entry
PDB id:
1s7b
Name: Transport protein
Title: Structure of the multidrug resistance efflux transporter emre from escherichia coli
Structure: Emre protein. Chain: a, b, c, d, e, f, g, h. Synonym: methyl viologen resistance protein c, ethidium resistance protein. Engineered: yes
Source: Escherichia coli. Bacteria. Gene: emre. Expressed in: escherichia coli.
Biol. unit: Tetramer (from PQS)
Resolution:
3.80Å     R-factor:   0.320     R-free:   0.350
Authors: C.Ma,G.Chang
Key ref:
C.Ma and G.Chang (2004). Structure of the multidrug resistance efflux transporter EmrE from Escherichia coli. Proc Natl Acad Sci U S A, 101, 2852-2857. PubMed id: 14970332 DOI: 10.1073/pnas.0400137101
Date:
29-Jan-04     Release date:   17-Feb-04    
PROCHECK
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 Headers
 References

Protein chains
Pfam   ArchSchema ?
P23895  (EMRE_ECOLI) -  Multidrug transporter EmrE
Seq:
Struc:
110 a.a.
106 a.a.
Key:    PfamA domain  Secondary structure

 

 
DOI no: 10.1073/pnas.0400137101 Proc Natl Acad Sci U S A 101:2852-2857 (2004)
PubMed id: 14970332  
 
 
Structure of the multidrug resistance efflux transporter EmrE from Escherichia coli.
C.Ma, G.Chang.
 
  ABSTRACT  
 
Multidrug resistance efflux transporters threaten to reverse the progress treating infectious disease by extruding a wide range of drug and other cytotoxic compounds. One such drug transporter, EmrE, from the small multidrug resistance family, utilizes proton gradients as an energy source to drive substrate translocation. In an effort to understand the molecular structural basis of this transport mechanism, we have determined the structure of EmrE from Escherichia coli to 3.8 A. EmrE is a tetramer comprised of two conformational heterodimers related by a pseudo two-fold symmetry axis perpendicular to the cell membrane. Based on the structure and biochemical evidence, we propose a mechanism by which EmrE accomplishes multidrug efflux by coupling conformational changes between two heterodimers with proton gradient. Because of its simplicity and compact size, the structure of EmrE can serve as an ideal model for understanding the general structural basis of proton:drug antiport for other drug efflux systems.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Amino acid sequence alignment of EmrE from E. coli shown with other homologs from human pathogens produced by using the program CLUSTALW (59). Conserved residues are colored according to their acidic (red), basic (blue), polar (green), or hydrophobic (gray) character. The -helices from the EmrE crystal structure are indicated, as well as the position of Glu-14, by an asterisk. The following National Center for Biotechnology Information accession codes were used for the alignment: E. coli,NP_415075; Staphylococcus aureus,NP_863640; Mycobacterium tuberculosis,NP_217581; Bacillus anthracis,NP_657212; Yersinia pestis, NP_405870 [GenBank] ; and Bacillus subtilis, NP_389612 [GenBank] and NP_389611 [GenBank] .
Figure 3.
Fig. 3. Structure of EmrE. (A) Side stereoview of EmrE. EmrE is a tetramer composed of two structural heterodimers. Each heterodimer contains subunits with different conformations. NH[3] and COOH termini are indicated. The residue Glu-14 is shown in red spheres. (B) Stereoview of superimposed C^ traces of subunits of the structural heterodimer are red and blue. (C) Surface representation of EmrE highlighting the drug translocation pathway. (D) Stereoview close-ups of the pair of Helix-1s at the interface between structural heterodimers are shown with black ribbons. Residues that abolish EmrE activity when replaced with cysteines are indicated with red spheres for Glu-14 and yellow for Leu-7, Ala-10, Ile-11, Gly-17, and Thr-18. All figures were prepared by using the programs PYMOL (www.pymol.org) or VMD (60) and were rendered with POV-RAY (www.povray.org).
 
  Figures were selected by the author.  
 
 
    Author's comment    
 
  Retracted by Chang et al. (2006) Science, 314, 187.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19224913 B.E.Poulsen, A.Rath, and C.M.Deber (2009).
The assembly motif of a bacterial small multidrug resistance protein.
  J Biol Chem, 284, 9870-9875.  
19171975 P.D.Jeffrey (2009).
Analysis of errors in the structure determination of MsbA.
  Acta Crystallogr D Biol Crystallogr, 65, 193-199.  
19265398 S.Balaz (2009).
Modeling kinetics of subcellular disposition of chemicals.
  Chem Rev, 109, 1793-1899.  
19721076 T.May, A.Ito, and S.Okabe (2009).
Induction of multidrug resistance mechanism in Escherichia coli biofilms by interplay between tetracycline and ampicillin resistance genes.
  Antimicrob Agents Chemother, 53, 4628-4639.  
19171974 V.M.Korkhov, and C.G.Tate (2009).
An emerging consensus for the structure of EmrE.
  Acta Crystallogr D Biol Crystallogr, 65, 186-192.  
18059473 S.Steiner-Mordoch, M.Soskine, D.Solomon, D.Rotem, A.Gold, M.Yechieli, Y.Adam, and S.Schuldiner (2008).
Parallel topology of genetically fused EmrE homodimers.
  EMBO J, 27, 17-26.  
18384529 W.Sherman, and B.Tidor (2008).
Novel method for probing the specificity binding profile of ligands: applications to HIV protease.
  Chem Biol Drug Des, 71, 387-407.  
17928292 A.Yan, Z.Guan, and C.R.Raetz (2007).
An undecaprenyl phosphate-aminoarabinose flippase required for polymyxin resistance in Escherichia coli.
  J Biol Chem, 282, 36077-36089.  
17429392 C.F.Higgins (2007).
Multiple molecular mechanisms for multidrug resistance transporters.
  Nature, 446, 749-757.  
17284035 S.F.Poget, S.M.Cahill, and M.E.Girvin (2007).
Isotropic bicelles stabilize the functional form of a small multidrug-resistance pump for NMR structural studies.
  J Am Chem Soc, 129, 2432-2433.  
17452106 S.Schuldiner (2007).
When biochemistry meets structural biology: the cautionary tale of EmrE.
  Trends Biochem Sci, 32, 252-258.  
18024586 Y.J.Chen, O.Pornillos, S.Lieu, C.Ma, A.P.Chen, and G.Chang (2007).
X-ray structure of EmrE supports dual topology model.
  Proc Natl Acad Sci U S A, 104, 18999-19004.
PDB codes: 3b5d 3b61 3b62
16828280 C.G.Tate (2006).
Comparison of three structures of the multidrug transporter EmrE.
  Curr Opin Struct Biol, 16, 457-464.  
16506075 D.Basting, I.Lehner, M.Lorch, and C.Glaubitz (2006).
Investigating transport proteins by solid state NMR.
  Naunyn Schmiedebergs Arch Pharmacol, 372, 451-464.  
16460819 D.M.Klaus, and H.N.Howard (2006).
Antibiotic efficacy and microbial virulence during space flight.
  Trends Biotechnol, 24, 131-136.  
16635801 J.J.Barker (2006).
Antibacterial drug discovery and structure-based design.
  Drug Discov Today, 11, 391-404.  
16462808 J.U.Bowie (2006).
Flip-flopping membrane proteins.
  Nat Struct Mol Biol, 13, 94-96.  
16381841 M.H.Saier, C.V.Tran, and R.D.Barabote (2006).
TCDB: the Transporter Classification Database for membrane transport protein analyses and information.
  Nucleic Acids Res, 34, D181-D186.  
16429150 M.Rapp, E.Granseth, S.Seppälä, and G.von Heijne (2006).
Identification and evolution of dual-topology membrane proteins.
  Nat Struct Mol Biol, 13, 112-116.  
16501047 S.G.Aller, and V.M.Unger (2006).
Projection structure of the human copper transporter CTR1 at 6-A resolution reveals a compact trimer with a novel channel-like architecture.
  Proc Natl Acad Sci U S A, 103, 3627-3632.  
16822664 S.J.Fleishman, and N.Ben-Tal (2006).
Progress in structure prediction of alpha-helical membrane proteins.
  Curr Opin Struct Biol, 16, 496-504.  
16406532 S.J.Fleishman, V.M.Unger, and N.Ben-Tal (2006).
Transmembrane protein structures without X-rays.
  Trends Biochem Sci, 31, 106-113.  
16212506 A.R.Osborne, T.A.Rapoport, and B.van den Berg (2005).
Protein translocation by the Sec61/SecY channel.
  Annu Rev Cell Dev Biol, 21, 529-550.  
15501941 C.W.Sikora, and R.J.Turner (2005).
Investigation of ligand binding to the multidrug resistance protein EmrE by isothermal titration calorimetry.
  Biophys J, 88, 475-482.  
15996519 J.M.Pagès, M.Masi, and J.Barbe (2005).
Inhibitors of efflux pumps in Gram-negative bacteria.
  Trends Mol Med, 11, 382-389.  
16015376 K.R.Vinothkumar, S.H.Smits, and W.Kühlbrandt (2005).
pH-induced structural change in a sodium/proton antiporter from Methanococcus jannaschii.
  EMBO J, 24, 2720-2729.  
15583400 C.Ma, and G.Chang (2004).
Crystallography of the integral membrane protein EmrE from Escherichia coli.
  Acta Crystallogr D Biol Crystallogr, 60, 2399-2402.  
15590782 E.Zientz, T.Dandekar, and R.Gross (2004).
Metabolic interdependence of obligate intracellular bacteria and their insect hosts.
  Microbiol Mol Biol Rev, 68, 745-770.  
15189838 K.E.Gottschalk, M.Soskine, S.Schuldiner, and H.Kessler (2004).
A structural model of EmrE, a multi-drug transporter from Escherichia coli.
  Biophys J, 86, 3335-3348.  
15231793 M.A.Warren, L.M.Kucharski, A.Veenstra, L.Shi, P.F.Grulich, and M.E.Maguire (2004).
The CorA Mg2+ transporter is a homotetramer.
  J Bacteriol, 186, 4605-4612.  
15313233 M.J.Lemieux, Y.Huang, and D.N.Wang (2004).
The structural basis of substrate translocation by the Escherichia coli glycerol-3-phosphate transporter: a member of the major facilitator superfamily.
  Curr Opin Struct Biol, 14, 405-412.  
15313232 S.H.White, and G.von Heijne (2004).
The machinery of membrane protein assembly.
  Curr Opin Struct Biol, 14, 397-404.  
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 codes are shown on the right.