Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator

  title={Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator},
  author={Ehmke Pohl and Jon C. Haller and Ana Mijovilovich and Wolfram Meyer‐Klaucke and Elspeth F. Garman and Michael L. Vasil},
  journal={Molecular Microbiology},
Iron is an essential element for almost all organisms, although an overload of this element results in toxicity because of the formation of hydroxyl radicals. Consequently, most living entities have developed sophisticated mechanisms to control their intracellular iron concentration. In many bacteria, including the opportunistic pathogen Pseudomonas aeruginosa, this task is performed by the ferric uptake regulator (Fur). Fur controls a wide variety of basic physiological processes including… 
Crystal Structure and Function of the Zinc Uptake Regulator FurB from Mycobacterium tuberculosis*
The crystal structure of FurB from Mycobacterium tuberculosis is reported and it is revealed that M. tuberculosis FurB is Zn(II)-dependent and is likely to control genes involved in the bacterial zinc uptake.
Iron Binding Site in a Global Regulator in Bacteria - Ferric Uptake Regulator (Fur) Protein: Structure, Mössbauer Properties, and Functional Implication.
Results of the first quantum chemical investigation of various first- and second-shell models and experimental Mössbauer data of E. Coli Fur are presented, including the first robust evidence that site 2 is the Fe binding site with a 3His/2Glu ligand set, being the first case in non-heme proteins.
Ferric uptake regulator protein: Binding free energy calculations and per‐residue free energy decomposition
Simulation results suggest that the formerly proposed site 2 is, in fact, the regulatory iron‐sensing site, and free energy decomposition analysis reveals a number of amino acids potentially important in dimerization and in DNA binding.
The structure of the Helicobacter pylori ferric uptake regulator Fur reveals three functional metal binding sites
DNA protection and circular dichroism experiments demonstrate that, while these two sites influence the affinity of HpFur for DNA, only one is absolutely required for DNA binding and could be responsible for the conformational changes of Fur upon metal binding while the other is a secondary site.
Variation on a theme: investigating the structural repertoires used by ferric uptake regulators to control gene expression
A comprehensive overview of the crystal structure of Fur family metalloregulators is presented with a specific focus on the new structures of these TFs bound to DNA.
New insights into the tetrameric family of the Fur metalloregulators
Another tetrameric structure of a PaFur mutant containing manganese and zinc metal ions is described and it is proposed that some conserved residues prevent the tetramerization in the subfamily of dimeric Fur.
Crystal structure of the Vibrio cholerae ferric uptake regulator (Fur) reveals insights into metal co‐ordination
The crystal structure of V. cholerae Fur is presented that reveals a very different orientation of the DNA‐binding domains compared with that observed in Pseudomonas aeruginosa Fur, suggesting that in fact the Zn2 site is the regulatory iron binding site and theZn1 site plays an auxiliary role.
Functional specialization within the Fur family of metalloregulators
There is a tremendous diversity in metal selectivity and biological function within the Fur family which includes sensors of iron (Fur), zinc (Zur), manganese (Mur), and nickel (Nur), and the mechanism of metal ion sensing by Fur family proteins is still controversial.
Quaternary Structure of Fur Proteins, a New Subfamily of Tetrameric Proteins.
This study purified Fur from four pathogenic strains and compared them to Fur from Escherichia coli, and showed that the dissociation of the tetramers into dimers is necessary for binding of Fur to DNA, and that this dissociation requires the combined effect of metal ion binding and DNA proximity.
The conformational stability and thermodynamics of Fur A (ferric uptake regulator) from Anabaena sp. PCC 7119.
The stability, thermodynamics and structure of the functional dimeric Fur A from Anabaena sp.


Crystal structure of the iron-dependent regulator (IdeR) from Mycobacterium tuberculosis shows both metal binding sites fully occupied.
The IdeR structure in complex with Zinc reported here is, however, the first wild-type repressor structure with both metal binding sites fully occupied, and reveals that both Met10 and most probably the Sgamma of Cys102 are ligands of the second metal binding site.
Crystal Structure of the Iron-dependent Regulator from Mycobacterium tuberculosis at 2.0-Å Resolution Reveals the Src Homology Domain 3-like Fold and Metal Binding Function of the Third Domain*
Clear, unbiased electron density was revealed for the Src homology domain 3-like third domain, which is often invisible in structures of iron-dependent regulators, and might be important in metal-dependent activation.
The ferric uptake regulation (Fur) repressor is a zinc metalloprotein.
It is reported here that the purified protein contains tightly bound zinc and proposed that Zn(II) is bound to the protein in vivo and suggested that many literature descriptions of purified Fur protein do not correspond to the apo-protein, but to Zn1Fur or Zn2Fur.
Iron metabolism in pathogenic bacteria.
The biochemistry of the bacterial cell can accommodate the challenges from the host and agents that interfere with bacterial iron metabolism may prove extremely valuable for chemotherapy of diseases.
Conformational changes of the ferric uptake regulation protein upon metal activation and DNA binding; first evidence of structural homologies with the diphtheria toxin repressor.
Fur and DtxR (diphtheria toxin repressor), another bacterial repressor, share not only the function of being iron concentration regulators, and the structure of their DNA-binding domain, with a non-classical helix-turn-helix motif is proposed.
Molecular characterization of the ferric-uptake regulator, fur, from Staphylococcus aureus.
The data suggest that Fur regulates iron-transport processes in S. aureus and partially complemented a fur- mutation in Bacillus subtilis.
Iron and metal regulation in bacteria.
  • K. Hantke
  • Biology
    Current opinion in microbiology
  • 2001
Identification of the two zinc-bound cysteines in the ferric uptake regulation protein from Escherichia coli: chemical modification and mass spectrometry analysis.
Examination of the sequence comprising the zinc site indicates that it may belong to a new type of structural zinc site, and Cys132 was shown to be the fastest reacting cysteine, implying it is a surface-exposed residue.
X-ray absorption spectroscopy of a new zinc site in the fur protein from Escherichia coli.
The present study provides the first unambiguous evidence for the presence of a structural zinc site in the Fur protein from Escherichia coli.
Role of iron in regulation of virulence genes
Studies of the mechanisms of regulation of iron acquisition systems and virulence determinants by iron should lead to a better understanding of the adaptive response of bacteria to the low-iron environment of the host and its importance in virulence.