Nitric oxide signalling by the bacterial enhancer binding protein NorR

在动物和人类中由一氧化氮合酶合成的一氧化氮在信号通路和保护免受入侵的细菌病原体中具有多种作用。一氧化氮是由被称为巨噬细胞的专门人类细胞产生的高浓度物质，用于毒害被吞噬的细菌或肿瘤细胞。细菌已经进化出特定的机制来保护自己免受一氧化氮的毒性作用，并修复由它引起的一些损伤。感受一氧化氮的调节蛋白通过激活各种酶的表达来提供主要反应，这些酶可以解毒这种分子。我们已经发现，一氧化氮直接与细菌调节蛋白相互作用，以激活一氧化氮解毒所需的基因表达。光谱研究表明，单个一氧化氮分子与蛋白质中的亚铁结合，而不是与血红素基团结合。我们的目标是了解一氧化氮与调节蛋白中的铁中心的结合如何激活开关，使细菌能够防御这种分子的毒性作用。

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.