gyrase

DNA gyrase is a bacterial type II topoisomerase that introduces negative supercoils into double-stranded DNA using energy from ATP hydrolysis. This activity helps compact the chromosome and facilitates DNA replication and transcription by counteracting the buildup of positive supercoils ahead of advancing polymerases.

The enzyme is a heterotetramer composed of two GyrA and two GyrB subunits (A2B2). GyrA carries the DNA cleavage-religation center, including the active-site tyrosine that forms a transient double-strand break in the DNA. GyrB contains the ATPase domain that powers the conformational changes necessary for strand passage. During catalysis, the enzyme creates a transient double-strand break in a segment of DNA (the G-segment), passes another segment (the T-segment) through the break, and then reseals the DNA, resulting in net negative supercoiling of the genome.

In vivo, gyrase introduces negative supercoils and also helps relieve positive supercoiling generated during replication and transcription. It is essential for bacterial viability in most species. Eukaryotes do not possess DNA gyrase; they rely on related type II topoisomerases for similar tasks.

DNA gyrase is a major target of antibiotics. Fluoroquinolones, including ciprofloxacin and levofloxacin, inhibit the resealing step by stabilizing the gyrase–DNA complex, causing DNA fragmentation and bacterial death. Other inhibitors, such as novobiocin, target the GyrB ATPase activity. Resistance commonly arises from mutations in gyrA or gyrB, which reduce drug binding, as well as from efflux mechanisms or plasmid-mediated resistance.