Staphylococcus aureus DNA gyrase (DNA gyrase)

Staphylococcus aureus DNA gyrase is an essential type II topoisomerase enzyme responsible for managing the topological state of DNA during replication and transcription (Source: PubMed, PMC6136625). It functions by introducing negative supercoils into the DNA molecule, a process driven by ATP hydrolysis, which relieves the torsional strain that accumulates ahead of the replication fork (Source: UniProt, P0A0K8). The enzyme is a heterotetramer composed of two GyrA and two GyrB subunits, where GyrA handles DNA breakage and rejoining while GyrB provides the energy via its ATPase domain (Source: Nature Reviews Microbiology). In the context of disease, this enzyme is a critical target for treating S. aureus infections, including methicillin-resistant strains (MRSA), which cause significant morbidity and mortality worldwide (Source: NIH, StatPearls). Fluoroquinolone antibiotics, such as ciprofloxacin, target DNA gyrase by stabilizing the covalent enzyme-DNA cleavage complex, effectively turning the enzyme into a cellular toxin that causes lethal double-strand breaks (Source: Journal of Antimicrobial Chemotherapy). However, the emergence of resistance through mutations in the quinolone resistance-determining regions (QRDR) of the gyrA and gyrB genes poses a major therapeutic challenge (Source: CDC).

Other names

DNA topoisomerase IIGyrA/GyrB complexType II topoisomeraseDNA topoisomerase 2-alpha/beta

Inhibition of the enzyme's ability to ligate DNA strands after cleavage, leading to the accumulation of double-strand breaks and bacterial cell death; some inhibitors also compete with ATP for binding to the GyrB subunit to block catalytic activity.