PDBsum entry 2gfp

Go to PDB code: 
protein Protein-protein interface(s) links
Membrane protein PDB id
Protein chains
375 a.a. *
* Residue conservation analysis
PDB id:
Name: Membrane protein
Title: Structure of the multidrug transporter emrd from escherichia coli
Structure: Multidrug resistance protein d. Chain: a, b. Synonym: emrd. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Gene: emrd. Expressed in: escherichia coli. Expression_system_taxid: 562
3.50Å     R-factor:   0.270     R-free:   0.350
Authors: Y.Yin,X.He,P.Szewczyk,T.Nguyen,G.Chang
Key ref:
Y.Yin et al. (2006). Structure of the multidrug transporter EmrD from Escherichia coli. Science, 312, 741-744. PubMed id: 16675700 DOI: 10.1126/science.1125629
22-Mar-06     Release date:   16-May-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P31442  (EMRD_ECOLI) -  Multidrug resistance protein D
394 a.a.
375 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     transport   4 terms 
  Biochemical function     drug transmembrane transporter activity     1 term  


DOI no: 10.1126/science.1125629 Science 312:741-744 (2006)
PubMed id: 16675700  
Structure of the multidrug transporter EmrD from Escherichia coli.
Y.Yin, X.He, P.Szewczyk, T.Nguyen, G.Chang.
EmrD is a multidrug transporter from the Major Facilitator Superfamily that expels amphipathic compounds across the inner membrane of Escherichia coli. Here, we report the x-ray structure of EmrD determined to a resolution of 3.5 angstroms. The structure reveals an interior that is composed mostly of hydrophobic residues, which is consistent with its role transporting amphipathic molecules. Two long loops extend into the inner leaflet side of the cell membrane. This region can serve to recognize and bind substrate directly from the lipid bilayer. We propose that multisubstrate specificity, binding, and transport are facilitated by these loop regions and the internal cavity.
  Selected figure(s)  
Figure 1.
Fig. 1. Stereoimages of crystallography and structure of EmrD. (A) A portion of the experimental electron density map is shown for H3, H6, and L6-7. The map is contoured to 1 . (B) Side view of EmrD. The N and C termini are indicated. (C) View of EmrD looking toward the cytoplasm showing the molecular two-fold axis relating the N- and C-terminal halves. Transmembrane helices are indicated. The images were created by PyMol (33).
Figure 3.
Fig. 3. A potential mechanism for hydrophobic substrate transport by EmrD. (A) The drug can enter the internal cavity of the transporter either through the inner membrane leaflet (path 1) or through the cytoplasm (path 2). Substrate recognition and binding may be facilitated through the selectivity filter and the internal cavity containing hydrophobic residues. (B) The drug is transported through a rocker-switch alternating-access model coupled with H+ antiport. (C) The drug is transported across the lipid bilayer.
  The above figures are reprinted by permission from the AAAs: Science (2006, 312, 741-744) copyright 2006.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
23075985 L.Sun, X.Zeng, C.Yan, X.Sun, X.Gong, Y.Rao, and N.Yan (2012).
Crystal structure of a bacterial homologue of glucose transporters GLUT1-4.
  Nature, 490, 361-366.
PDB codes: 4gby 4gbz 4gc0
20938980 K.Illergård, A.Kauko, and A.Elofsson (2011).
Why are polar residues within the membrane core evolutionary conserved?
  Proteins, 79, 79-91.  
21131908 S.Newstead, D.Drew, A.D.Cameron, V.L.Postis, X.Xia, P.W.Fowler, J.C.Ingram, E.P.Carpenter, M.S.Sansom, M.J.McPherson, S.A.Baldwin, and S.Iwata (2011).
Crystal structure of a prokaryotic homologue of the mammalian oligopeptide-proton symporters, PepT1 and PepT2.
  EMBO J, 30, 417-426.
PDB code: 2xut
21315728 S.Radestock, and L.R.Forrest (2011).
The alternating-access mechanism of MFS transporters arises from inverted-topology repeats.
  J Mol Biol, 407, 698-715.  
21220112 Y.Sonoda, S.Newstead, N.J.Hu, Y.Alguel, E.Nji, K.Beis, S.Yashiro, C.Lee, J.Leung, A.D.Cameron, B.Byrne, S.Iwata, and D.Drew (2011).
Benchmarking membrane protein detergent stability for improving throughput of high-resolution X-ray structures.
  Structure, 19, 17-25.  
19883765 A.Alisio, and M.Mueckler (2010).
Purification and characterization of mammalian glucose transporters expressed in Pichia pastoris.
  Protein Expr Purif, 70, 81-87.  
19923217 A.Eudes, E.R.Kunji, A.Noiriel, S.M.Klaus, T.J.Vickers, S.M.Beverley, J.F.Gregory, and A.D.Hanson (2010).
Identification of transport-critical residues in a folate transporter from the folate-biopterin transporter (FBT) family.
  J Biol Chem, 285, 2867-2875.  
20730247 A.Grove (2010).
Urate-responsive MarR homologs from Burkholderia.
  Mol Biosyst, 6, 2133-2142.  
  20052679 A.Schlessinger, P.Matsson, J.E.Shima, U.Pieper, S.W.Yee, L.Kelly, L.Apeltsin, R.M.Stroud, T.E.Ferrin, K.M.Giacomini, and A.Sali (2010).
Comparison of human solute carriers.
  Protein Sci, 19, 412-428.  
20009031 B.Thorens, and M.Mueckler (2010).
Glucose transporters in the 21st Century.
  Am J Physiol Endocrinol Metab, 298, E141-E145.  
19819701 D.A.Gutmann, A.Ward, I.L.Urbatsch, G.Chang, and H.W.van Veen (2010).
Understanding polyspecificity of multidrug ABC transporters: closing in on the gaps in ABCB1.
  Trends Biochem Sci, 35, 36-42.  
20006622 H.Zheng, J.Taraska, A.J.Merz, and T.Gonen (2010).
The prototypical H+/galactose symporter GalP assembles into functional trimers.
  J Mol Biol, 396, 593-601.  
  20544010 J.Luo, and S.M.Parsons (2010).
Conformational Propensities of Peptides Mimicking Transmembrane Helix 5 and Motif C in Wild-type and Mutant Vesicular Acetylcholine Transporters.
  ACS Chem Neurosci, 1, 381-390.  
19826804 K.McLuskey, A.W.Roszak, Y.Zhu, and N.W.Isaacs (2010).
Crystal structures of all-alpha type membrane proteins.
  Eur Biophys J, 39, 723-755.  
20667175 K.R.Vinothkumar, and R.Henderson (2010).
Structures of membrane proteins.
  Q Rev Biophys, 43, 65.  
20565143 L.Ruiz-Pavón, P.M.Karlsson, J.Carlsson, D.Samyn, B.Persson, B.L.Persson, and C.Spetea (2010).
Functionally important amino acids in the Arabidopsis thylakoid phosphate transporter: homology modeling and site-directed mutagenesis.
  Biochemistry, 49, 6430-6439.  
20225888 P.Khare, A.M.Ojeda, A.Chandrasekaran, and S.M.Parsons (2010).
Possible important pair of acidic residues in vesicular acetylcholine transporter.
  Biochemistry, 49, 3049-3059.  
20877283 S.Dang, L.Sun, Y.Huang, F.Lu, Y.Liu, H.Gong, J.Wang, and N.Yan (2010).
Structure of a fucose transporter in an outward-open conformation.
  Nature, 467, 734-738.
PDB codes: 3o7p 3o7q
20204450 S.J.Facey, and A.Kuhn (2010).
Biogenesis of bacterial inner-membrane proteins.
  Cell Mol Life Sci, 67, 2343-2362.  
21151967 S.Mohan, A.Sheena, N.Poulose, and G.Anilkumar (2010).
Molecular dynamics simulation studies of GLUT4: substrate-free and substrate-induced dynamics and ATP-mediated glucose transport inhibition.
  PLoS One, 5, e14217.  
20861838 X.He, P.Szewczyk, A.Karyakin, M.Evin, W.X.Hong, Q.Zhang, and G.Chang (2010).
Structure of a cation-bound multidrug and toxic compound extrusion transporter.
  Nature, 467, 991-994.
PDB codes: 3mkt 3mku
20821001 Y.M.Weaver, and B.Hagenbuch (2010).
Several conserved positively charged amino acids in OATP1B1 are involved in binding or translocation of different substrates.
  J Membr Biol, 236, 279-290.  
19720022 C.J.Law, G.Enkavi, D.N.Wang, and E.Tajkhorshid (2009).
Structural basis of substrate selectivity in the glycerol-3-phosphate: phosphate antiporter GlpT.
  Biophys J, 97, 1346-1353.  
19722844 H.I.Zgurskaya (2009).
Multicomponent drug efflux complexes: architecture and mechanism of assembly.
  Future Microbiol, 4, 919-932.  
19231985 H.Nikaido (2009).
Multidrug resistance in bacteria.
  Annu Rev Biochem, 78, 119-146.  
19798434 J.Jeon, J.S.Yang, and S.Kim (2009).
Integration of evolutionary features for the identification of functionally important residues in major facilitator superfamily transporters.
  PLoS Comput Biol, 5, e1000522.  
19207745 J.L.Martinez, M.B.Sánchez, L.Martínez-Solano, A.Hernandez, L.Garmendia, A.Fajardo, and C.Alvarez-Ortega (2009).
Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems.
  FEMS Microbiol Rev, 33, 430-449.  
20041202 K.Kapoor, M.Rehan, A.Kaushiki, R.Pasrija, A.M.Lynn, and R.Prasad (2009).
Rational mutational analysis of a multidrug MFS transporter CaMdr1p of Candida albicans by employing a membrane environment based computational approach.
  PLoS Comput Biol, 5, e1000624.  
19449892 M.Mueckler, and C.Makepeace (2009).
Model of the exofacial substrate-binding site and helical folding of the human Glut1 glucose transporter based on scanning mutagenesis.
  Biochemistry, 48, 5934-5942.  
19706416 M.S.Yousef, and L.Guan (2009).
A 3D structure model of the melibiose permease of Escherichia coli represents a distinctive fold for Na+ symporters.
  Proc Natl Acad Sci U S A, 106, 15291-15296.  
19685929 P.Khare, A.R.White, and S.M.Parsons (2009).
Multiple protonation states of vesicular acetylcholine transporter detected by binding of [3H]vesamicol.
  Biochemistry, 48, 8965-8975.  
19678712 X.Z.Li, and H.Nikaido (2009).
Efflux-mediated drug resistance in bacteria: an update.
  Drugs, 69, 1555-1623.  
19878597 Y.M.Tse, M.Yu, and J.S.Tsang (2009).
Topological analysis of a haloacid permease of a Burkholderia sp. bacterium with a PhoA-LacZ reporter.
  BMC Microbiol, 9, 233.  
18690707 C.Gui, and B.Hagenbuch (2008).
Amino acid residues in transmembrane domain 10 of organic anion transporting polypeptide 1B3 are critical for cholecystokinin octapeptide transport.
  Biochemistry, 47, 9090-9097.  
18537473 C.J.Law, P.C.Maloney, and D.N.Wang (2008).
Ins and outs of major facilitator superfamily antiporters.
  Annu Rev Microbiol, 62, 289-305.  
18981181 D.M.Blodgett, C.Graybill, and A.Carruthers (2008).
Analysis of glucose transporter topology and structural dynamics.
  J Biol Chem, 283, 36416-36424.  
18559978 I.Lasry, B.Berman, R.Straussberg, Y.Sofer, H.Bessler, M.Sharkia, F.Glaser, G.Jansen, S.Drori, and Y.G.Assaraf (2008).
A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function.
  Blood, 112, 2055-2061.  
18223078 K.A.Hassan, T.Souhani, R.A.Skurray, and M.H.Brown (2008).
Analysis of tryptophan residues in the staphylococcal multidrug transporter QacA reveals long-distance functional associations of residues on opposite sides of the membrane.
  J Bacteriol, 190, 2441-2449.  
18927357 S.Weyand, T.Shimamura, S.Yajima, S.Suzuki, O.Mirza, K.Krusong, E.P.Carpenter, N.G.Rutherford, J.M.Hadden, J.O'Reilly, P.Ma, M.Saidijam, S.G.Patching, R.J.Hope, H.T.Norbertczak, P.C.Roach, S.Iwata, P.J.Henderson, and A.D.Cameron (2008).
Structure and molecular mechanism of a nucleobase-cation-symport-1 family transporter.
  Science, 322, 709-713.
PDB codes: 2jln 2jlo
18452311 X.Wang, L.Ye, C.C.McKinney, M.Feng, and P.C.Maloney (2008).
Cysteine scanning mutagenesis of TM5 reveals conformational changes in OxlT, the oxalate transporter of Oxalobacter formigenes.
  Biochemistry, 47, 5709-5717.  
17429392 C.F.Higgins (2007).
Multiple molecular mechanisms for multidrug resistance transporters.
  Nature, 446, 749-757.  
17211682 C.J.De Feo, S.G.Aller, and V.M.Unger (2007).
A structural perspective on copper uptake in eukaryotes.
  Biometals, 20, 705-716.  
17915951 C.J.Law, Q.Yang, C.Soudant, P.C.Maloney, and D.N.Wang (2007).
Kinetic evidence is consistent with the rocker-switch mechanism of membrane transport by GlpT.
  Biochemistry, 46, 12190-12197.  
17473876 C.Miller (2007).
A leak in the EAATs.
  Nat Struct Mol Biol, 14, 356-357.  
17925435 I.Smirnova, V.Kasho, J.Y.Choe, C.Altenbach, W.L.Hubbell, and H.R.Kaback (2007).
Sugar binding induces an outward facing conformation of LacY.
  Proc Natl Acad Sci U S A, 104, 16504-16509.  
17660252 J.Almqvist, Y.Huang, A.Laaksonen, D.N.Wang, and S.Hovmöller (2007).
Docking and homology modeling explain inhibition of the human vesicular glutamate transporters.
  Protein Sci, 16, 1819-1829.  
17320103 J.B.Klauda, and B.R.Brooks (2007).
Sugar binding in lactose permease: anomeric state of a disaccharide influences binding structure.
  J Mol Biol, 367, 1523-1534.  
17566106 L.Bamber, M.Harding, M.Monné, D.J.Slotboom, and E.R.Kunji (2007).
The yeast mitochondrial ADP/ATP carrier functions as a monomer in mitochondrial membranes.
  Proc Natl Acad Sci U S A, 104, 10830-10834.  
17881559 L.Guan, O.Mirza, G.Verner, S.Iwata, and H.R.Kaback (2007).
Structural determination of wild-type lactose permease.
  Proc Natl Acad Sci U S A, 104, 15294-15298.
PDB code: 2v8n
17334909 L.H.Matherly, Z.Hou, and Y.Deng (2007).
Human reduced folate carrier: translation of basic biology to cancer etiology and therapy.
  Cancer Metastasis Rev, 26, 111-128.  
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
16923166 A.Chandrasekaran, A.M.Ojeda, N.G.Kolmakova, and S.M.Parsons (2006).
Mutational and bioinformatics analysis of proline- and glycine-rich motifs in vesicular acetylcholine transporter.
  J Neurochem, 98, 1551-1559.  
17417701 H.Jung, T.Pirch, and D.Hilger (2006).
Secondary transport of amino acids in prokaryotes.
  J Membr Biol, 213, 119-133.  
16958854 K.A.Hassan, M.Galea, J.Wu, B.A.Mitchell, R.A.Skurray, and M.H.Brown (2006).
Functional effects of intramembranous proline substitutions in the staphylococcal multidrug transporter QacA.
  FEMS Microbiol Lett, 263, 76-85.  
17056710 L.Bamber, M.Harding, P.J.Butler, and E.R.Kunji (2006).
Yeast mitochondrial ADP/ATP carriers are monomeric in detergents.
  Proc Natl Acad Sci U S A, 103, 16224-16229.  
16856936 O.Lewinson, J.Adler, N.Sigal, and E.Bibi (2006).
Promiscuity in multidrug recognition and transport: the bacterial MFS Mdr transporters.
  Mol Microbiol, 61, 277-284.  
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.