DNA gyrase–DNA cleavage-ligation complex (DNA gyrase)

DNA gyrase is an essential bacterial enzyme belonging to the type II topoisomerase family, responsible for introducing negative supercoils into DNA (Nature Reviews Microbiology, 2014). This process is critical for relieving torsional strain during DNA replication and transcription, as well as for DNA decatenation (PubMed, PMC2447884). The enzyme functions by forming a transient, covalent DNA gyrase–DNA cleavage-ligation complex where it creates a double-strand break in the DNA, passes another DNA duplex through the gap, and subsequently reseals the break (Journal of Biological Chemistry, 2010). This specific intermediate complex is the primary pharmacological target for fluoroquinolone antibiotics, which bind to the enzyme-DNA interface and stabilize the cleaved state (PNAS, 2014). By preventing the ligation step, these drugs cause the accumulation of permanent double-strand breaks, leading to bacterial cell death (StatPearls, 2023). Since DNA gyrase is found only in bacteria and not in humans, it serves as a highly effective and selective target for treating a wide range of bacterial infections, although its utility is increasingly threatened by the development of chromosomal mutations in the gyrA and gyrB subunits (Microbiology and Molecular Biology Reviews, 2010).

Other names

GyraseBacterial topoisomerase IIGyrA-GyrB complexDNA topoisomerase (ATP-hydrolysing)DNA gyrase cleavage complex

Stabilization of the covalent DNA-protein cleavage complex and inhibition of DNA ligation, leading to lethal double-strand breaks.