title: Crystal structure of the Vibrio cholerae ferric uptake regulator (Fur) reveals insights into metal co-ordination.
abstract: The ferric uptake regulator (Fur) is a metal-dependent DNA-binding protein that acts as both a repressor and an activator of numerous genes involved in maintaining iron homeostasis in bacteria. It has also been demonstrated in Vibrio cholerae that Fur plays an additional role in pathogenesis, opening up the potential of Fur as a drug target for cholera. Here we present the crystal structure of V. cholerae Fur that reveals a very different orientation of the DNA-binding domains compared with that observed in Pseudomonas aeruginosa Fur. Each monomer of the dimeric Fur protein contains two metal binding sites occupied by zinc in the crystal structure. In the P. aeruginosa study these were designated as the regulatory site (Zn1) and structural site (Zn2). This V. cholerae Fur study, together with studies on Fur homologues and paralogues, suggests that in fact the Zn2 site is the regulatory iron binding site and the Zn1 site plays an auxiliary role. There is no evidence of metal binding to the cysteines that are conserved in many Fur homologues, including Escherichia coli Fur. An analysis of the metal binding properties shows that V. cholerae Fur can be activated by a range of divalent metals.
authors.affiliation: Centre for Biomolecular Sciences, University of St Andrews, St Andrews, Fife KY16 9ST, UK.
authors.forename: Md Arif
authors.initials: MA
authors.lastname: Sheikh
authors.forename: Garry L
authors.initials: GL
authors.lastname: Taylor
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D003001:Cloning, Molecular; D008667:Metalloproteins / Q000737:chemistry*; D008670:Metals / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000737:chemistry*; D014734:Vibrio cholerae / Q000737:chemistry* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D008667:Metalloproteins; D008670:Metals; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial