Significance: In bacteria, transcriptional responses to reactive oxygen and nitrogen species (ROS and RNS, respectively) are typically coordinated by regulatory proteins that employ metal centers or reactive thiols to detect the presence of those species. This review is focused on the structure, function and mechanism of three regulatory proteins (Fur, PerR, and NorR) that contain non-heme iron and regulate the transcription of target genes in response to ROS and/or RNS. The targets for regulation include genes encoding detoxification activities, and genes encoding proteins involved in the repair of the damage caused by ROS and RNS.
Recent advances: Three-dimensional structures of several Fur proteins and of PerR are revealing important details of the metal binding sites of these proteins, showing a surprising degree of structural diversity in the Fur family.
Critical issues: Discussion of the interaction of Fur with ROS and RNS will illustrate the difficulty that sometimes exists in distinguishing between true physiological responses and adventitious reactions of a regulatory protein with a reactive ligand.
Future directions: Consideration of these three sensor proteins illuminates some of the key questions that remain unanswered, for example, the nature of the biochemical determinants that dictate the sensitivity and specificity of the interaction of the sensor proteins with their cognate signals.