DNA gyrase subunit A (GyrA) (GyrA)

DNA gyrase subunit A (GyrA) is a critical enzyme in Pseudomonas aeruginosa that belongs to the type II topoisomerase family [10]. It functions as a heterotetramer (A2B2) with subunit B to introduce negative supercoils into double-stranded DNA, a process essential for relieving torsional strain during DNA replication, transcription, and repair [10, 12]. GyrA specifically mediates the breakage and rejoining of DNA strands [6, 7]. In clinical practice, GyrA is the primary target for fluoroquinolone antibiotics such as ciprofloxacin and levofloxacin, which stabilize the enzyme-DNA cleavage complex and cause lethal double-strand breaks [1, 7]. However, P. aeruginosa frequently develops resistance through point mutations in the quinolone resistance-determining region (QRDR) of the gyrA gene, most commonly at positions Thr-83 and Asp-87 [1, 2, 3]. These mutations reduce the binding affinity of the drugs, posing a significant challenge in treating infections, particularly in immunocompromised patients or those with cystic fibrosis [1, 14].

Other names

DNA gyrase subunit AGyrADNA topoisomerase II subunit APA3168

Inhibition of DNA gyrase activity by binding to the GyrA protein/enzyme-DNA complex, preventing re-ligation of cleaved DNA strands, leading to double-strand DNA breaks and inhibition of bacterial DNA replication [1, 6, 7].