spacer
spacer

PDBsum entry 2onj
Go to PDB code: 
protein ligands metals Protein-protein interface(s) links
Hydrolase PDB id
2onj

 

 

 

 

Loading ...

 
JSmol PyMol  
Contents
Protein chains
578 a.a. *
Ligands
ANP ×2
Metals
_NA ×4
Waters ×20
* Residue conservation analysis
PDB id:
2onj
Name: Hydrolase
Title: Structure of the multidrug abc transporter sav1866 from s. Aureus in complex with amp-pnp
Structure: Multidrug export atp-binding/permease protein sav1866. Chain: a, b. Engineered: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
3.40Å     R-factor:   0.254     R-free:   0.278
Authors: R.J.P.Dawson,K.P.Locher
Key ref: R.J.Dawson and K.P.Locher (2007). Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP. Febs Lett, 581, 935-938. PubMed id: 17303126
Date:
24-Jan-07     Release date:   13-Mar-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q99T13  (Y1866_STAAM) -  Putative multidrug export ATP-binding/permease protein SAV1866 from Staphylococcus aureus (strain Mu50 / ATCC 700699)
Seq:
Struc: 		 
Seq:
Struc: 		578 a.a.
578 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.7.6.2.-  - ?????
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

 

 
Febs Lett 581:935-938 (2007)
PubMed id: 17303126  
 
 
Structure of the multidrug ABC transporter Sav1866 from Staphylococcus aureus in complex with AMP-PNP.
R.J.Dawson, K.P.Locher.
 
  ABSTRACT  
 
Staphylococcus aureus Sav1866 is a bacterial homolog of the human ABC transporter Mdr1 that causes multidrug resistance in cancer cells. We report the crystal structure of Sav1866 in complex with adenosine-5'-(beta,gamma-imido)triphosphate (AMP-PNP) at 3.4A resolution and compare it with the previously determined structure of Sav1866 with bound ADP. Besides differences in the ATP-binding sites, no significant conformational changes were observed. The results confirm that the ATP-bound state of multidrug ABC transporters is coupled to an outward-facing conformation of the transmembrane domains.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22447242 M.Hohl, C.Briand, M.G.Grütter, and M.A.Seeger (2012).
Crystal structure of a heterodimeric ABC transporter in its inward-facing conformation.
  Nat Struct Mol Biol, 19, 395-402.
PDB code: 3qf4
23000901 V.M.Korkhov, S.A.Mireku, and K.P.Locher (2012).
Structure of AMP-PNP-bound vitamin B12 transporter BtuCD-F.
  Nature, 490, 367-372.
PDB code: 4fi3
  21488101 A.S.Oliveira, A.M.Baptista, and C.M.Soares (2011).
Conformational changes induced by ATP-hydrolysis in an ABC transporter: A molecular dynamics study of the Sav1866 exporter.
  Proteins, 79, 1977-1990.  
20855293 B.Meineke, B.Schwer, R.Schaffrath, and S.Shuman (2011).
Determinants of eukaryal cell killing by the bacterial ribotoxin PrrC.
  Nucleic Acids Res, 39, 687-700.  
21194365 R.P.Gupta, P.Kueppers, L.Schmitt, and R.Ernst (2011).
The multidrug transporter Pdr5: a molecular diode?
  Biol Chem, 392, 53-60.  
20061384 A.Siarheyeva, R.Liu, and F.J.Sharom (2010).
Characterization of an asymmetric occluded state of P-glycoprotein with two bound nucleotides: implications for catalysis.
  J Biol Chem, 285, 7575-7586.  
21059948 C.Orelle, F.J.Alvarez, M.L.Oldham, A.Orelle, T.E.Wiley, J.Chen, and A.L.Davidson (2010).
Dynamics of alpha-helical subdomain rotation in the intact maltose ATP-binding cassette transporter.
  Proc Natl Acad Sci U S A, 107, 20293-20298.  
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.  
20655344 D.W.Urry, K.D.Urry, W.Szaflarski, and M.Nowicki (2010).
Elastic-contractile model proteins: Physical chemistry, protein function and drug design and delivery.
  Adv Drug Deliv Rev, 62, 1404-1455.  
19961542 E.Crowley, and R.Callaghan (2010).
Multidrug efflux pumps: drug binding--gates or cavity?
  FEBS J, 277, 530-539.  
19961540 I.D.Kerr, P.M.Jones, and A.M.George (2010).
Multidrug efflux pumps: the structures of prokaryotic ATP-binding cassette transporter efflux pumps and implications for our understanding of eukaryotic P-glycoproteins and homologues.
  FEBS J, 277, 550-563.  
20454684 J.Aittoniemi, H.de Wet, F.M.Ashcroft, and M.S.Sansom (2010).
Asymmetric switching in a homodimeric ABC transporter: a simulation study.
  PLoS Comput Biol, 6, e1000762.  
20652498 J.S.Ham, S.G.Lee, S.G.Jeong, M.H.Oh, D.H.Kim, T.Lee, B.Y.Lee, S.H.Yoon, and H.Kim (2010).
Powerful usage of phylogenetically diverse Staphylococcus aureus control strains for detecting multidrug resistance genes in transcriptomics studies.
  Mol Cells, 30, 71-76.  
20799350 L.Kelly, H.Fukushima, R.Karchin, J.M.Gow, L.W.Chinn, U.Pieper, M.R.Segal, D.L.Kroetz, and A.Sali (2010).
Functional hot spots in human ATP-binding cassette transporter nucleotide binding domains.
  Protein Sci, 19, 2110-2121.  
20715055 R.Doshi, B.Woebking, and H.W.van Veen (2010).
Dissection of the conformational cycle of the multidrug/lipidA ABC exporter MsbA.
  Proteins, 78, 2867-2872.  
19921465 S.Igarashi, M.Osawa, S.Ozawa, and I.Shimada (2010).
Backbone resonance assignments for the ligand binding subunit of the histidine permease complex (HisJ) from Escherichia coli, under histidine-bound and unbound states.
  Biomol NMR Assign, 4, 17-20.  
19927121 V.Kanelis, R.P.Hudson, P.H.Thibodeau, P.J.Thomas, and J.D.Forman-Kay (2010).
NMR evidence for differential phosphorylation-dependent interactions in WT and DeltaF508 CFTR.
  EMBO J, 29, 263-277.  
  21078867 Z.Kopeikin, Y.Sohma, M.Li, and T.C.Hwang (2010).
On the mechanism of CFTR inhibition by a thiazolidinone derivative.
  J Gen Physiol, 136, 659-671.  
19132955 A.Siarheyeva, and F.J.Sharom (2009).
The ABC transporter MsbA interacts with lipid A and amphipathic drugs at different sites.
  Biochem J, 419, 317-328.  
19114108 A.Ward, S.Mulligan, B.Carragher, G.Chang, and R.A.Milligan (2009).
Nucleotide dependent packing differences in helical crystals of the ABC transporter MsbA.
  J Struct Biol, 165, 169-175.  
19124053 C.A.McDevitt, R.Collins, I.D.Kerr, and R.Callaghan (2009).
Purification and structural analyses of ABCG2.
  Adv Drug Deliv Rev, 61, 57-65.  
19339978 D.C.Gadsby (2009).
Ion channels versus ion pumps: the principal difference, in principle.
  Nat Rev Mol Cell Biol, 10, 344-352.  
19234479 D.C.Rees, E.Johnson, and O.Lewinson (2009).
ABC transporters: the power to change.
  Nat Rev Mol Cell Biol, 10, 218-227.  
19019987 D.Dietrich, H.Schmuths, C.d.e. .M.Lousa, J.M.Baldwin, S.A.Baldwin, A.Baker, F.L.Theodoulou, and M.J.Holdsworth (2009).
Mutations in the Arabidopsis peroxisomal ABC transporter COMATOSE allow differentiation between multiple functions in planta: insights from an allelic series.
  Mol Biol Cell, 20, 530-543.  
18957373 D.Muallem, and P.Vergani (2009).
Review. ATP hydrolysis-driven gating in cystic fibrosis transmembrane conductance regulator.
  Philos Trans R Soc Lond B Biol Sci, 364, 247-255.  
19053133 D.Parcej, and R.Tampé (2009).
Solute-binding sites in ABC transporters for recognition, occlusion and trans-inhibition.
  ChemMedChem, 4, 25-28.  
18955484 H.T.Lin, V.N.Bavro, N.P.Barrera, H.M.Frankish, S.Velamakanni, H.W.van Veen, C.V.Robinson, M.I.Borges-Walmsley, and A.R.Walmsley (2009).
MacB ABC Transporter Is a Dimer Whose ATPase Activity and Macrolide-binding Capacity Are Regulated by the Membrane Fusion Protein MacA.
  J Biol Chem, 284, 1145-1154.  
18990670 J.Aittoniemi, C.Fotinou, T.J.Craig, H.de Wet, P.Proks, and F.M.Ashcroft (2009).
Review. SUR1: a unique ATP-binding cassette protein that functions as an ion channel regulator.
  Philos Trans R Soc Lond B Biol Sci, 364, 257-267.  
19159494 J.P.Becker, G.Depret, F.Van Bambeke, P.M.Tulkens, and M.Prévost (2009).
Molecular models of human P-glycoprotein in two different catalytic states.
  BMC Struct Biol, 9, 3.  
19707853 J.P.Mornon, P.Lehn, and I.Callebaut (2009).
Molecular models of the open and closed states of the whole human CFTR protein.
  Cell Mol Life Sci, 66, 3469-3486.  
19254551 J.Weng, J.Ma, K.Fan, and W.Wang (2009).
Asymmetric conformational flexibility in the ATP-binding cassette transporter HI1470/1.
  Biophys J, 96, 1918-1930.  
18957379 K.P.Locher (2009).
Review. Structure and mechanism of ATP-binding cassette transporters.
  Philos Trans R Soc Lond B Biol Sci, 364, 239-245.  
19937827 M.A.Demel, O.Krämer, P.Ettmayer, E.E.Haaksma, and G.F.Ecker (2009).
Predicting ligand interactions with ABC transporters in ADME.
  Chem Biodivers, 6, 1960-1969.  
19395376 M.Grote, Y.Polyhach, G.Jeschke, H.J.Steinhoff, E.Schneider, and E.Bordignon (2009).
Transmembrane signaling in the maltose ABC transporter MalFGK2-E: periplasmic MalF-P2 loop communicates substrate availability to the ATP-bound MalK dimer.
  J Biol Chem, 284, 17521-17526.  
19748784 P.M.Jones, M.L.O'Mara, and A.M.George (2009).
ABC transporters: a riddle wrapped in a mystery inside an enigma.
  Trends Biochem Sci, 34, 520-531.  
19054062 Q.Li, Q.Jiang, E.Pfendner, A.Váradi, and J.Uitto (2009).
Pseudoxanthoma elasticum: clinical phenotypes, molecular genetics and putative pathomechanisms.
  Exp Dermatol, 18, 1.  
19366916 R.D.Cannon, E.Lamping, A.R.Holmes, K.Niimi, P.V.Baret, M.V.Keniya, K.Tanabe, M.Niimi, A.Goffeau, and B.C.Monk (2009).
Efflux-mediated antifungal drug resistance.
  Clin Microbiol Rev, 22, 291.  
19265398 S.Balaz (2009).
Modeling kinetics of subcellular disposition of chemicals.
  Chem Rev, 109, 1793-1899.  
18535149 A.L.Davidson, E.Dassa, C.Orelle, and J.Chen (2008).
Structure, function, and evolution of bacterial ATP-binding cassette systems.
  Microbiol Mol Biol Rev, 72, 317.  
18281290 A.P.Babenko (2008).
A novel ABCC8 (SUR1)-dependent mechanism of metabolism-excitation uncoupling.
  J Biol Chem, 283, 8778-8782.  
18175303 C.Globisch, I.K.Pajeva, and M.Wiese (2008).
Identification of putative binding sites of P-glycoprotein based on its homology model.
  ChemMedChem, 3, 280-295.  
18405843 G.F.Ecker, T.Stockner, and P.Chiba (2008).
Computational models for prediction of interactions with ABC-transporters.
  Drug Discov Today, 13, 311-317.  
18489584 I.Carrier, and P.Gros (2008).
Investigating the role of the invariant carboxylate residues E552 and E1197 in the catalytic activity of Abcb1a (mouse Mdr3).
  FEBS J, 275, 3312-3324.  
17951296 J.Weng, J.Ma, K.Fan, and W.Wang (2008).
The conformational coupling and translocation mechanism of vitamin B12 ATP-binding cassette transporter BtuCD.
  Biophys J, 94, 612-621.  
18093977 J.Y.Lee, I.L.Urbatsch, A.E.Senior, and S.Wilkens (2008).
Nucleotide-induced structural changes in P-glycoprotein observed by electron microscopy.
  J Biol Chem, 283, 5769-5779.  
19053284 K.M.Westfahl, J.A.Merten, A.H.Buchaklian, and C.S.Klug (2008).
Functionally important ATP binding and hydrolysis sites in Escherichia coli MsbA.
  Biochemistry, 47, 13878-13886.  
18508776 L.Cebotaru, N.Vij, I.Ciobanu, J.Wright, T.Flotte, and W.B.Guggino (2008).
Cystic fibrosis transmembrane regulator missing the first four transmembrane segments increases wild type and DeltaF508 processing.
  J Biol Chem, 283, 21926-21933.  
18721111 M.A.Demel, R.Schwaha, O.Krämer, P.Ettmayer, E.E.Haaksma, and G.F.Ecker (2008).
In silico prediction of substrate properties for ABC-multidrug transporters.
  Expert Opin Drug Metab Toxicol, 4, 1167-1180.  
18948194 M.L.Oldham, A.L.Davidson, and J.Chen (2008).
Structural insights into ABC transporter mechanism.
  Curr Opin Struct Biol, 18, 726-733.  
18790847 P.C.Wen, and E.Tajkhorshid (2008).
Dimer opening of the nucleotide binding domains of ABC transporters after ATP hydrolysis.
  Biophys J, 95, 5100-5110.  
18644782 S.Pagant, E.Y.Brovman, J.J.Halliday, and E.A.Miller (2008).
Mapping of interdomain interfaces required for the functional architecture of Yor1p, a eukaryotic ATP-binding cassette (ABC) transporter.
  J Biol Chem, 283, 26444-26451.  
18093093 U.Mamat, T.C.Meredith, P.Aggarwal, A.Kühl, P.Kirchhoff, B.Lindner, A.Hanuszkiewicz, J.Sun, O.Holst, and R.W.Woodard (2008).
Single amino acid substitutions in either YhjD or MsbA confer viability to 3-deoxy-d-manno-oct-2-ulosonic acid-depleted Escherichia coli.
  Mol Microbiol, 67, 633-648.  
18024585 A.Ward, C.L.Reyes, J.Yu, C.B.Roth, and G.Chang (2007).
Flexibility in the ABC transporter MsbA: Alternating access with a twist.
  Proc Natl Acad Sci U S A, 104, 19005-19010.
PDB codes: 3b5w 3b5x 3b5y 3b5z 3b60
18025464 H.de Wet, M.G.Rees, K.Shimomura, J.Aittoniemi, A.M.Patch, S.E.Flanagan, S.Ellard, A.T.Hattersley, M.S.Sansom, and F.M.Ashcroft (2007).
Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes.
  Proc Natl Acad Sci U S A, 104, 18988-18992.  
17578454 R.J.Dawson, K.Hollenstein, and K.P.Locher (2007).
Uptake or extrusion: crystal structures of full ABC transporters suggest a common mechanism.
  Mol Microbiol, 65, 250-257.  
17673622 R.N.Hvorup, B.A.Goetz, M.Niederer, K.Hollenstein, E.Perozo, and K.P.Locher (2007).
Asymmetry in the structure of the ABC transporter-binding protein complex BtuCD-BtuF.
  Science, 317, 1387-1390.
PDB code: 2qi9
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.

 

spacer
spacer