Homology between CAP and Fnr, a regulator of anaerobic respiration in Escherichia coli

The fnr gene is essential for the expression of anaerobic respiratory metabolism in Escherichia coli. Genetic and biochemical studies support the view that its product, Fnr, is a transcriptional regulatory protein specific for genes encoding anaerobic respiratory functions (fumarate, nitrate and nitrite reductases, hydrogenase, etc.). In this respect Fnr may be considered analogous to the wellcharacterized catabolite gene activator protein (CAP), which mediates the control of catabolite-sensitive gene transcription. With a view to identifying its function, the fnr gene has recently been cloned and the primary structure of the Fnr protein deduced from the nucleotide sequence. This has revealed the presence of three regions of sequence homology with CAP. One corresponds to the DNA-binding site, a region of about 20 highly conserved amino acids that is believed to form a characteristic three-dimensional structure in several transcriptional regulators. The other regions of homology are in the nucleotide binding domain of CAP but the residues that interact with cAMP are not identical in Fnr. These homologies suggest that Fnr and CAP may have similar three-dimensional structures and that the regulation of anaerobic energy metabolism may involve interaction between Fnr and an unidentified effector molecule.