title: Mechanism of oxygen sensing by the bacterial transcription factor fumarate-nitrate reduction (FNR).
abstract: The facultative anaerobe Escherichia coli adopts different metabolic modes in response to the availability of oxygen. The global transcriptional regulator FNR (fumarate-nitrate reduction) monitors the availability of oxygen in the environment. Binding as a homodimer to palindromic sequences of DNA, FNR carries a sensory domain, remote from the DNA binding helix-turn-helix motif, which responds to oxygen. The sensing mechanism involves the transformation of a [4Fe-4S](2+) cluster into a [2Fe-2S] form in vitro on reaction with oxygen. Evidence is presented to show that this process proceeds by at least two steps, the first, an oxidative one, being the formation, on reaction with O(2), of a [3Fe-4S](1+) cluster as an intermediate accompanied by the production of hydrogen peroxide. This is followed by a slower, non-redox, pseudo-first order step in which the [3Fe-4S](1+) form converts to a [2Fe-2S](2+) cluster. This must be accompanied by a substantial protein conformational change since the four cysteine ligands that bind the two forms of the FeS clusters have different spatial disposition. Hydrogen peroxide is also an oxidant of the [4Fe-4S](2+), causing a similar cluster transformation to a [2Fe-2S] form. Either the hydrogen peroxide formed on reaction with oxygen can be recycled by intracellular catalase or it can be used to oxidize further Fe-S clusters. In both cases, the efficacy of oxygen sensing by FNR will be increased.
authors.affiliation: School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, NR4 7TJ.
authors.forename: Jason
authors.initials: J
authors.lastname: Crack
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Green
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thomson
mesh_terms: D004268:DNA-Binding Proteins / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C060704:FNR protein, E coli; D007506:Iron-Sulfur Proteins; D006861:Hydrogen Peroxide; D010100:Oxygen