Structure analysis of Bacillus cereus MepR-like transcription regulator, BC0657, in complex with pseudo-ligand...

The MarR family of transcriptional regulatory proteins in bacteria and archaea respond to environmental changes and regulate transcriptional processes by ligand binding or cysteine oxidation. MepR belongs to the MarR family, and its mutations are associated with the development of multidrug resistances, causing a growing health problem. Therefore, it has been of great interest to locate the ligand binding site of MepR and reveal the ligand-mediated transcriptional regulation mechanism. Here, we report on the crystal structure of Bacillus cereus MepR-like transcription factor, BC0657, at 2.16 Å resolution. Interestingly, BC0657 was complexed with fortuitous pseudo-ligands, which were assessed to be lipid molecules containing a long fatty acid, rather than phenolic compounds previously observed in other MarR proteins. The BC0657-ligand interaction provides the first molecular view of how MepR recognizes ligands to respond to toxic chemicals. Moreover, our comparative structure analyses of ligand binding sites on BC0657 and its homologs suggest that transcriptional repression by MepR would be relieved by ligand-induced changes in dimerization organization.