Mode of action of GR122222X, a novel inhibitor of bacterial DNA gyrase

Abstract

GR122222X is a potent inhibitor of the supercoiling reaction of bacterial DNA gyrase. We show that this compound binds stoichiometrically to inactivate the ATPase activity of a 43-kDa N-terminal fragment of the B subunit and competitively inhibits the binding of a radiolabelled coumarin drug to N- terminal fragments of GyrB. These and other data suggest that GR122222X has a mode of action similar, but not identical, to that of coumarin antibiotics.