Molecular basis of halorespiration control by CprK, a CRP‐FNR type transcriptional regulator

Summary Certain bacteria are able to conserve energy via the reductive dehalogenation of halo‐organic compounds in a respiration‐type metabolism. The transcriptional regulator CprK from Desulfitobacterium spp. induces expression of halorespiratory genes upon binding of o‐chlorophenol ligands and is reversibly inactivated by oxygen through disulphide bond formation. We report crystal structures of D. hafniense CprK in the ligand‐free (both oxidation states), ligand‐bound (reduced) and DNA‐bound states, making it the first member of the widespread CRP‐FNR superfamily for which a complete structural description of both redox‐dependent and allosteric molecular rearrangements is available. In conjunction with kinetic and thermodynamic ligand binding studies, we provide a model for the allosteric mechanisms underpinning transcriptional control. Amino acids that play a key role in this mechanism are not conserved in functionally distinct CRP‐FNR members. This suggests that, despite significant structural homology, distinct allosteric mechanisms are used, enabling this protein family to control a very wide range of processes.