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PDBsum entry 1qkc
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protein ligands metals links
Tonb dependent receptor PDB id
1qkc

 

 

 

 

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Contents
Protein chain
707 a.a. *
Ligands
PA1-GCN-KDO-GMH-
GMH-GLC-GLC-GLC-
GLA-GMH-KDO
FTT ×2
FTT-FTT ×2
DPO ×2
PO4 ×2
ALB
Metals
_NI
Waters ×332
* Residue conservation analysis
PDB id:
1qkc
Name: Tonb dependent receptor
Title: Escherichia coli ferric hydroxamate uptake receptor (fhua) in complex delta two-albomycin
Structure: Ferric hydroxamate receptor. Chain: a. Synonym: fhua. Engineered: yes. Mutation: yes. Other_details: a hexahistidine tag plus five additional linker residues have been genetically inserted after residue 405 of the mature fhua sequence as an affinity tag
Source: Escherichia coli k-12. Organism_taxid: 83333. Strain: aw740. Variant: ra-chemotype. Cell: bacterial. Cellular_location: outer membrane. Gene: fhua. Expressed in: escherichia coli k-12. Expression_system_taxid: 83333.
Resolution:
3.10Å     R-factor:   0.222     R-free:   0.283
Authors: A.D.Ferguson,V.Braun,H.-P.Fiedler,J.W.Coulton,K.Diederichs,W.Welte
Key ref: A.D.Ferguson et al. (2000). Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA. Protein Sci, 9, 956-963. PubMed id: 10850805 DOI: 10.1110/ps.9.5.956
Date:
18-Jul-99     Release date:   05-Jun-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
P06971  (FHUA_ECOLI) -  Ferrichrome outer membrane transporter/phage receptor from Escherichia coli (strain K12)
Seq:
Struc: 		 
Seq:
Struc: 		747 a.a.
707 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 11 residue positions (black crosses)

 

 
DOI no: 10.1110/ps.9.5.956 Protein Sci 9:956-963 (2000)
PubMed id: 10850805  
 
 
Crystal structure of the antibiotic albomycin in complex with the outer membrane transporter FhuA.
A.D.Ferguson, V.Braun, H.P.Fiedler, J.W.Coulton, K.Diederichs, W.Welte.
 
  ABSTRACT  
 
One alternative method for drug delivery involves the use of siderophore-antibiotic conjugates. These compounds represent a specific means by which potent antimicrobial agents, covalently linked to iron-chelating siderophores, can be actively transported across the outer membrane of gram-negative bacteria. These "Trojan Horse" antibiotics may prove useful as an efficient means to combat multi-drug-resistant bacterial infections. Here we present the crystallographic structures of the natural siderophore-antibiotic conjugate albomycin and the siderophore phenylferricrocin, in complex with the active outer membrane transporter FhuA from Escherichia coli. To our knowledge, this represents the first structure of an antibiotic bound to its cognate transporter. Albomycins are broad-host range antibiotics that consist of a hydroxamate-type iron-chelating siderophore, and an antibiotically active, thioribosyl pyrimidine moiety. As observed with other hydroxamate-type siderophores, the three-dimensional structure of albomycin reveals an identical coordination geometry surrounding the ferric iron atom. Unexpectedly, this antibiotic assumes two conformational isomers in the binding site of FhuA, an extended and a compact form. The structural information derived from this study provides novel insights into the diverse array of antibiotic moieties that can be linked to the distal portion of iron-chelating siderophores and offers a structural platform for the rational design of hydroxamate-type siderophore-antibiotic conjugates.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21455261 K.D.Krewulak, and H.J.Vogel (2011).
TonB or not TonB: is that the question?
  Biochem Cell Biol, 89, 87-97.  
21414201 N.Muhammad, T.Dworeck, M.Fioroni, and U.Schwaneberg (2011).
Engineering of the E. coli Outer Membrane Protein FhuA to overcome the Hydrophobic Mismatch in Thick Polymeric Membranes.
  J Nanobiotechnology, 9, 8.  
20147287 J.C.Grigg, J.D.Cooper, J.Cheung, D.E.Heinrichs, and M.E.Murphy (2010).
The Staphylococcus aureus siderophore receptor HtsA undergoes localized conformational changes to enclose staphyloferrin A in an arginine-rich binding pocket.
  J Biol Chem, 285, 11162-11171.
PDB codes: 3lhs 3li2
20420522 N.Noinaj, M.Guillier, T.J.Barnard, and S.K.Buchanan (2010).
TonB-dependent transporters: regulation, structure, and function.
  Annu Rev Microbiol, 64, 43-60.  
19772347 M.Sandy, and A.Butler (2009).
Microbial iron acquisition: marine and terrestrial siderophores.
  Chem Rev, 109, 4580-4595.  
19221879 T.A.Wencewicz, U.Möllmann, T.E.Long, and M.J.Miller (2009).
Is drug release necessary for antimicrobial activity of siderophore-drug conjugates? Syntheses and biological studies of the naturally occurring salmycin "Trojan Horse" antibiotics and synthetic desferridanoxamine-antibiotic conjugates.
  Biometals, 22, 633-648.  
19130258 V.Braun, A.Pramanik, T.Gwinner, M.Köberle, and E.Bohn (2009).
Sideromycins: tools and antibiotics.
  Biometals, 22, 3.  
19329642 V.Braun (2009).
FhuA (TonA), the career of a protein.
  J Bacteriol, 191, 3431-3436.  
17534527 A.Wilks, and K.A.Burkhard (2007).
Heme and virulence: how bacterial pathogens regulate, transport and utilize heme.
  Nat Prod Rep, 24, 511-522.  
17287889 C.S.López, and J.H.Crosa (2007).
Characterization of ferric-anguibactin transport in Vibrio anguillarum.
  Biometals, 20, 393-403.  
17973380 E.M.Nolan, M.A.Fischbach, A.Koglin, and C.T.Walsh (2007).
Biosynthetic tailoring of microcin E492m: post-translational modification affords an antibacterial siderophore-peptide conjugate.
  J Am Chem Soc, 129, 14336-14347.  
17804665 M.Miethke, and M.A.Marahiel (2007).
Siderophore-based iron acquisition and pathogen control.
  Microbiol Mol Biol Rev, 71, 413-451.  
17785509 N.Beckloff, D.Laube, T.Castro, D.Furgang, S.Park, D.Perlin, D.Clements, H.Tang, R.W.Scott, G.N.Tew, and G.Diamond (2007).
Activity of an antimicrobial peptide mimetic against planktonic and biofilm cultures of oral pathogens.
  Antimicrob Agents Chemother, 51, 4125-4132.  
16707680 A.Pramanik, and V.Braun (2006).
Albomycin uptake via a ferric hydroxamate transport system of Streptococcus pneumoniae R6.
  J Bacteriol, 188, 3878-3886.  
16718603 D.Destoumieux-Garzón, J.Peduzzi, X.Thomas, C.Djediat, and S.Rebuffat (2006).
Parasitism of iron-siderophore receptors of Escherichia coli by the siderophore-peptide microcin E492m and its unmodified counterpart.
  Biometals, 19, 181-191.  
16927281 M.Nallani, O.Onaca, N.Gera, K.Hildenbrand, W.Hoheisel, and U.Schwaneberg (2006).
A nanophosphor-based method for selective DNA recovery in Synthosomes.
  Biotechnol J, 1, 828-834.  
16927262 O.Onaca, M.Nallani, S.Ihle, A.Schenk, and U.Schwaneberg (2006).
Functionalized nanocompartments (Synthosomes): limitations and prospective applications in industrial biotechnology.
  Biotechnol J, 1, 795-805.  
16718599 R.S.Peacock, V.V.Andrushchenko, A.R.Demcoe, M.Gehmlich, L.S.Lu, A.G.Herrero, and H.J.Vogel (2006).
Characterization of TonB interactions with the FepA cork domain and FecA N-terminal signaling domain.
  Biometals, 19, 127-142.  
16874469 T.Olczak (2006).
Analysis of conserved glutamate residues in Porphyromonas gingivalis outer membrane receptor HmuR: toward a further understanding of heme uptake.
  Arch Microbiol, 186, 393-402.  
15739205 D.P.Chimento, R.J.Kadner, and M.C.Wiener (2005).
Comparative structural analysis of TonB-dependent outer membrane transporters: implications for the transport cycle.
  Proteins, 59, 240-251.  
15487950 C.Wandersman, and P.Delepelaire (2004).
Bacterial iron sources: from siderophores to hemophores.
  Annu Rev Microbiol, 58, 611-647.  
15231815 F.Endriss, and V.Braun (2004).
Loop deletions indicate regions important for FhuA transport and receptor functions in Escherichia coli.
  J Bacteriol, 186, 4818-4823.  
15109731 J.Langenscheid, H.Killmann, and V.Braun (2004).
A FhuA mutant of Escherichia coli is infected by phage T1-independent of TonB.
  FEMS Microbiol Lett, 234, 133-137.  
15102756 K.H.Rohde, and D.W.Dyer (2004).
Analysis of haptoglobin and hemoglobin-haptoglobin interactions with the Neisseria meningitidis TonB-dependent receptor HpuAB by flow cytometry.
  Infect Immun, 72, 2494-2506.  
15162482 N.K.Natt, H.Kaur, and G.P.Raghava (2004).
Prediction of transmembrane regions of beta-barrel proteins using ANN- and SVM-based methods.
  Proteins, 56, 11-18.  
12944258 J.D.Faraldo-Gómez, G.R.Smith, and M.S.Sansom (2003).
Molecular dynamics simulations of the bacterial outer membrane protein FhuA: a comparative study of the ferrichrome-free and bound states.
  Biophys J, 85, 1406-1420.  
12563288 J.D.Faraldo-Gómez, and M.S.Sansom (2003).
Acquisition of siderophores in gram-negative bacteria.
  Nat Rev Mol Cell Biol, 4, 105-116.  
12829269 S.C.Andrews, A.K.Robinson, and F.Rodríguez-Quiñones (2003).
Bacterial iron homeostasis.
  FEMS Microbiol Rev, 27, 215-237.  
12364374 J.L.Martínez, and F.Baquero (2002).
Interactions among strategies associated with bacterial infection: pathogenicity, epidemicity, and antibiotic resistance.
  Clin Microbiol Rev, 15, 647-679.  
11415317 C.Hilty, and M.Winterhalter (2001).
Facilitated substrate transport through membrane proteins.
  Phys Rev Lett, 86, 5624-5627.  
11344156 H.Killmann, M.Braun, C.Herrmann, and V.Braun (2001).
FhuA barrel-cork hybrids are active transporters and receptors.
  J Bacteriol, 183, 3476-3487.  
11171005 V.Braun, C.Bös, M.Braun, and H.Killmann (2001).
Outer membrane channels and active transporters for the uptake of antibiotics.
  J Infect Dis, 183, S12-S16.  
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.

 

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