Structure and Activities of Escherichia coli DNA Gyrase

In 1976, Gellert et al. (1976a) described a novel enzyme from Escherichia coli, termed DNA gyrase, that introduced negative supercoils into closed, duplex DNA in the presence of ATP. Two related roles of the enzyme were apparent. First, gyrase could put the DNA of the cell under negative superhelical tension, a state that facilitates the binding of a number of enzymes (for review, see Wang 1978). Second, gyrase might relieve the twisting stress that is generated by the obligatory uncoiling of the plectonemic double helix during DNA synthesis; it was recognized by Watson and Crick (1953) in their description of DNA 25 years ago that the “difficulty of untwisting is a formidable one.” Gyrase was directly linked to DNA replication by Gellert et al. (1976b), who found that two related drugs that inhibit DNA synthesis, novobiocin and coumermycin A1, also inhibited gyrase. Resistance to these antibiotics is controlled by the...