Nitric oxide signalling by the bacterial enhancer binding protein NorR

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Nitric oxide, synthesised in animals and humans by the nitric oxide synthases, has multiple roles in signalling pathways and in protecting against invading bacterial pathogens. Nitric oxide is produced at high concentrations by specialised human cells known as macrophages to poison engulfed bacteria or tumor cells. Bacteria have evolved specific mechanisms to defend themselves against the toxic effects of nitric oxide and to repair some of the damage caused by it. Regulatory proteins that sense nitric oxide provide the primary response by activating the expression of various enzymes that can detoxify this molecule. We have discovered that nitric oxide interacts directly with a bacterial regulatory protein to activate expression of genes required for nitric oxide detoxification. Spectroscopic studies demonstrate that a single molecule of nitric oxide binds to ferrous iron in the protein, rather than to a haem group. We aim to understand how the binding of nitric oxide to the iron centre in the regulatory protein activates the switch that allows bacteria to defend themselves against the toxic effects of this molecule.

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