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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2002

Direct inhibition by nitric oxide of the transcriptional ferric uptake regulation protein via nitrosylation of the iron

Résumé

Ferric uptake regulation protein (Fur) is a bacterial global regulator that uses iron as a cofactor to bind to specific DNA sequences. The function of Fur is not limited to iron homeostasis. A wide variety of genes involved in various mechanisms such as oxidative and acid stresses are under Fur control. Flavohemoglobin (Hmp) is an NO-detoxifying enzyme induced by NO and nitrosothiol compounds. Fur recently was found to regulate hmp in Salmonella typhimurium, and in Escherichia coli, the iron-chelating agent 2,2-dipyridyl induces hmp expression. We now establish direct inhibition of E. coli Fur activity by NO. By using chromosomal Fur-regulated lacZ reporter fusion in E. coli, Fur activity is switched off by NO at micromolar concentration. In vitro Fur DNA-binding activity, as measured by protection of restriction site in aerobactin promoter, is directly sensitive to NO. NO reacts with Fe II in purified FeFur protein to form a S ‫؍‬ 1͞2 low-spin FeFur-NO complex with a g ‫؍‬ 2.03 EPR signal. Appearance of the same EPR signal in NO-treated cells links nitrosylation of the iron with Fur inhibition. The nitrosylated Fur protein is still a dimer and is stable in anaerobiosis but slowly decays in air. This inhibition probably arises from a conformational switch, leading to an inactive dimeric protein. These data establish a link between control of iron metabolism and the response to NO effects.
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Dates et versions

hal-02975685 , version 1 (26-10-2020)

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Benoit d'Autreaux, Daniè Le Touati, Beate Bersch, Jean-Marc Latour, Isabelle Michaud-Soret. Direct inhibition by nitric oxide of the transcriptional ferric uptake regulation protein via nitrosylation of the iron. Proceedings of the National Academy of Sciences of the United States of America, 2002, 99 (26), pp.16619-24. ⟨10.1073/pnas.252591299⟩. ⟨hal-02975685⟩
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