It contains three domains: an N-terminal GAF (cGMP phosphodiesterase, adenylate cyclase, FhlA) domain that is involved in signal sensing [4, 12, 13]; a central catalytic AAA+ domain that is required for interacting with σ⁵⁴ and for coupling ATP hydrolysis to promoter DNA melting by RNA polymerase; and a C-terminal domain that contains a helix-turn-helix DNA-binding motif [14]. In the absence of NO, the activity of the central catalytic AAA+ domain of NorR is repressed by direct interaction between the GAF domain and the σ⁵⁴-interacting region of the AAA+ domain. This interaction prevents access to the σ⁵⁴-RNA polymerase complex [15]. Binding of NO relieves intramolecular repression and activates the ATPase activity of the central AAA+ domain [12, 16]. The GAF domain contains a mononuclear nonheme iron center that binds NO reversibly [12]. Spectroscopy studies and structural modeling of the GAF domain identified five candidate ligands for the nonheme iron and suggested a model in which it is coordinated in a pseudo-octahedral environment by three aspartate residues, an arginine, and a cysteine [14]. The iron oxidation state influences the activation of NorR [17]. The intergenic region of norR and norVW carries three binding sites for NorR with a symmetrical 11-bp consensus sequence [7]. These sites act as enhancer-binding sites for transcriptional activation by NorR [2, 18]. All three sites are required for the stimulation of the ATPase activity in vitro and activation of norV expression in vivo [19]. Based on biochemical experiments and electron micrographs using a norR mutant carrying a deletion of the N-terminal domain, it has been proposed that NorR binds as a hexameric ring to DNA [19]. The data further suggest that in contrast to other enhancer-binding proteins the DNA binding per se induces a conformational change in NorR that promotes hexameric ring formation. Presumably the hexamer is further stabilized by additional DNA wrapped around the ring. Binding of NO to the GAF domain relieves intramolecular repression of the central domain, leading to the activation of the ATPase activity and interaction with σ⁵⁴ RNA polymerase [19]. Reviews: [3, 16, 20]