A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3(2)

Brekasis, Dimitris and Paget, Mark S B (2003) A novel sensor of NADH/NAD+ redox poise in Streptomyces coelicolor A3(2). EMBO Journal, 22 (18). pp. 4856-4865. ISSN 0261-4189

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Abstract

We describe the identification of Rex, a novel redox-sensing repressor that appears to be widespread among Gram-positive bacteria. In Streptomyces coelicolor Rex binds to operator (ROP) sites located upstream of several respiratory genes, including the cydABCD and rex-hemACD operons. The DNA-binding activity of Rex appears to be controlled by the redox poise of the NADH/NAD+ pool. Using electromobility shift and surface plasmon resonance assays we show that NADH, but not NAD+, inhibits the DNA-binding activity of Rex. However, NAD+ competes with NADH for Rex binding, allowing Rex to sense redox poise over a range of NAD(H) concentrations. Rex is predicted to include a pyridine nucleotide-binding domain (Rossmann fold), and residues that might play key structural and nucleotide binding roles are highly conserved. In support of this, the central glycine in the signature motif (GlyXGlyXXGly) is shown to be essential for redox sensing. Rex homologues exist in most Gram-positive bacteria, including human pathogens such as Staphylococcus aureus, Listeria monocytogenes and Streptococcus pneumoniae.

Item Type: Article
Additional Information: Brekasis was a PhD student in Paget's lab when the work was conceived, carried out and written up. Brekasis performed all practical aspects under Paget's supervision and Paget wrote up the manuscript. The work describes for the first time a sensor of NADH/NAD+ redox poise in bacteria.
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Mark Paget
Date Deposited: 06 Feb 2012 20:26
Last Modified: 26 Jun 2012 14:46
URI: http://sro.sussex.ac.uk/id/eprint/25927
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