DNA gyrase (Escherichia coli) (DNA gyrase)

DNA gyrase is an essential bacterial enzyme in Escherichia coli that belongs to the type II topoisomerase family. It is a heterotetramer composed of two GyrA and two GyrB subunits, which together catalyze the introduction of negative supercoils into double-stranded DNA using energy derived from ATP hydrolysis (UniProt P0AES4, P0AES6). This activity is vital for relieving the torsional stress that accumulates ahead of the replication fork and transcription machinery, as well as for DNA decatenation (PubMed: 2563378). Because DNA gyrase is unique to bacteria and lacks a direct homolog in humans, it is a primary target for several classes of antibiotics, most notably the fluoroquinolones (StatPearls: NBK547703). These drugs, such as ciprofloxacin, stabilize the covalent enzyme-DNA intermediate, preventing DNA religation and leading to lethal double-strand breaks (PubChem CID 2764). Clinical utility is often hampered by the development of resistance, typically through point mutations in the quinolone resistance-determining regions (QRDR) of the gyrA and gyrB genes (PubMed: 12654733). Other inhibitors, such as aminocoumarins like novobiocin, target the ATP-binding site on the GyrB subunit to prevent the energy-dependent supercoiling process. Overall, the enzyme is a cornerstone of antibacterial therapy, though its efficacy is increasingly challenged by evolving bacterial defense mechanisms.

Other names

DNA topoisomerase IIGyrA-GyrB complexType II topoisomeraseDNA topoisomerase 2

Inhibition of DNA gyrase activity by stabilizing the enzyme-DNA cleavage complex or by competitive inhibition of the ATP-binding site on the GyrB subunit.