Pharmacogenic therapies targeting the metal-ion transcriptional regulation machinery in bacteria

摘要

The subject invention pertains to methods of identifying compounds that bind to a binding pocket on metal ion binding proteins of the ArsR/SmtB family and modulate their regulatory activity by increasing the propensity of the proteins to remain in a conformationally trapped form such as the metal ion bound conformation or disulfide-linked conformation, the DNA bound conformation, or the apo-conformation. The invention provides methods of identifying such compounds using computer software programs. The invention also provides bioassays for identifying such compounds. The invention also provides pharmaceutical compositions containing compounds that modulate metalloregulatory activities of the metal ion binding proteins of the ArsR/SmtB family.