DNA topoisomerase II (DNA gyrase) (DNA gyrase)

DNA gyrase is an essential bacterial enzyme in Escherichia coli belonging to the type II topoisomerase family (UniProt: P0AES4, P0AES6). It is a heterotetrameric protein composed of two GyrA and two GyrB subunits that catalyzes the introduction of negative supercoils into double-stranded DNA using energy derived from ATP hydrolysis (PubMed: 21115521). This function is critical for relieving the torsional strain that accumulates ahead of replication forks and transcription machinery, as well as for the decatenation of replicated chromosomes. Because DNA gyrase is unique to bacteria and lacks a direct human ortholog, it serves as a primary target for several classes of clinical antibiotics (StatPearls: NBK547703). Fluoroquinolones, the most prominent class of inhibitors, act by trapping the enzyme-DNA complex in a cleaved state, resulting in lethal DNA fragmentation and bacterial cell death. Other inhibitors, such as the aminocoumarins, target the ATPase activity of the GyrB subunit to prevent the enzyme's catalytic cycle (Wikipedia: DNA gyrase).

Other names

GyrA-GyrB complexType II topoisomeraseDNA topoisomerase (ATP-hydrolysing)Topoisomerase II

Fluoroquinolones inhibit DNA gyrase by stabilizing the covalent enzyme-DNA cleavage complex, which prevents the re-ligation of DNA strands and leads to lethal double-strand breaks (StatPearls: NBK547703). Aminocoumarins like novobiocin act as competitive inhibitors of the ATP-binding site on the GyrB subunit, preventing the energy-dependent supercoiling activity (PubMed: 21115521).