DNA gyrase (Helicobacter pylori) (DNA gyrase)

DNA gyrase is an essential type II topoisomerase in Helicobacter pylori that manages DNA topology by introducing negative supercoils into the circular chromosome (UniProt P56001, P56003). This ATP-dependent process is vital for DNA replication, transcription, and recombination, as it relieves the torsional strain that accumulates ahead of the replication fork (PubMed: 11133455). The enzyme is a heterotetramer composed of two GyrA subunits, which mediate DNA cleavage and rejoining, and two GyrB subunits, which provide energy through ATP hydrolysis (PubMed: 15659676). In the context of H. pylori infection, DNA gyrase is a critical therapeutic target for fluoroquinolone antibiotics like levofloxacin, which are frequently employed in second-line or "rescue" eradication regimens (StatPearls: Helicobacter Pylori). However, the clinical utility of these drugs is increasingly compromised by point mutations in the "quinolone resistance-determining region" (QRDR) of the gyrA gene, particularly at positions 87 and 91, which reduce drug binding affinity (PubMed: 25635015). Because DNA gyrase is unique to bacteria and lacks a direct human ortholog, it remains a high-priority target for the development of novel antimicrobial agents designed to overcome existing resistance mechanisms (PubMed: 30203134).

Other names

DNA topoisomerase IIGyrA/GyrB complexType II DNA topoisomerase

Inhibition of DNA gyrase prevents the relaxation of supercoiled DNA and the resolution of knots during replication, leading to the formation of stable drug-enzyme-DNA complexes that cause double-strand breaks and bacterial cell death (PubMed: 11133455).