title: The Metal-Dependent Regulators FurA and FurB from Mycobacterium Tuberculosis.
abstract: The ferric uptake regulators (Fur) form a large family of bacterial metal-activated DNA-binding proteins that control a diverse set of genes at the transcriptional level. Mycobacterium tuberculosis, the causative agent of tuberculosis, expresses two members of the Fur family, designated FurA and FurB. Although both belong to the same family, they share only approximately 25% sequence identity and as a consequence, they differ significantly in some of their key biological functions. FurA appears to be a specialized iron-dependent regulator that controls the katG gene, which encodes for a catalase-peroxidase involved in the response of M. tuberculosis to oxidative stress. KatG is also the key mycobacterial enzyme responsible for the activation of the first-line tuberculosis drug Isoniazid. FurB in contrast requires Zn(2+) rather than Fe(2+), to bind to its target sequence in regulated genes, which include those involved in Zn(2+)-homeostasis. Recent biochemical, crystallographic and spectroscopic data have now shed light on the activation and metal discrimination mechanisms in this protein family.
authors.affiliation: Cancer Research UK, Clare Hall Laboratories, London Research Institute, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3LD, UK.
authors.forename: Debora
authors.initials: D
authors.lastname: Lucarelli
authors.affiliation: Department of Microbiology, University of Colorado, Denver Anschutz Medical Campus, Aurora, CO 80045, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Vasil
authors.affiliation: European Molecular Biology Laboratory, Hamburg Outstation, Notkestr. 85, D-22603 Hamburg, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Meyer-Klaucke
authors.affiliation: Department of Chemistry & School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UK.
authors.forename: Ehmke
authors.initials: E
authors.lastname: Pohl