Structure of a biological oxygen sensor: A new mechanism for heme-driven signal transduction

The FixL proteins are biological oxygen sensors that restrict the expressio n of specific genes to hypoxic conditions. FixL's oxygen detecting domain i s a heme binding region that controls the activity of an attached histidine kinase. The FixL switch is regulated by binding of oxygen and other strong -field ligands. In the absence of bound ligand, the heme domain permits kin ase activity. In the presence of bound ligand, this domain turns off kinase activity. Comparison of the structures of two forms of the Bradyrhizobium japonicum FixL heme domain, one in the "on" state without bound ligand and one in the "off" state with bound cyanide, reveals a mechanism of regulatio n by a heme that is distinct from the classical hemoglobin models. The clos e structural resemblance of the FixL heme domain to the photoactive yellow protein confirms the existence of a PAS structural motif but reveals the pr esence of an alternative regulatory gateway.