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The Metal-Dependent Regulators FurA and FurB from Mycobacterium Tuberculosis
European Molecular Biology Laboratory, Hamburg Outstation, Notkestr. 85, D-22603 Hamburg, Germany
Department of Microbiology, University of Colorado, Denver Anschutz Medical Campus, Aurora, CO 80045, USA
Department of Chemistry & School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UK
Cancer Research UK, Clare Hall Laboratories, London Research Institute, Blanche Lane, South Mimms, Potters Bar, Herts EN6 3LD, UK
* Author to whom correspondence should be addressed.
Received: 9 May 2008; in revised form: 29 July 2008 / Accepted: 30 July 2008 / Published: 28 August 2008
Abstract: The ferric uptake regulators (Fur) form a large family of bacterial metalactivated 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 Zn2+ rather than Fe2+, to bind to its target sequence in regulated genes, which include those involved in Zn2+-homeostasis. Recent biochemical, crystallographic and spectroscopic data have now shed light on the activation and metal discrimination mechanisms in this protein family.
Keywords: Metal uptake; regulator; ferric; zinc; Mycobacterium tuberculosis
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MDPI and ACS Style
Lucarelli, D.; Vasil, M.L.; Meyer-Klaucke, W.; Pohl, E. The Metal-Dependent Regulators FurA and FurB from Mycobacterium Tuberculosis. Int. J. Mol. Sci. 2008, 9, 1548-1560.
Lucarelli D, Vasil ML, Meyer-Klaucke W, Pohl E. The Metal-Dependent Regulators FurA and FurB from Mycobacterium Tuberculosis. International Journal of Molecular Sciences. 2008; 9(8):1548-1560.
Lucarelli, Debora; Vasil, Michael L.; Meyer-Klaucke, Wolfram; Pohl, Ehmke. 2008. "The Metal-Dependent Regulators FurA and FurB from Mycobacterium Tuberculosis." Int. J. Mol. Sci. 9, no. 8: 1548-1560.