Bacterial DNA gyrase subunit A (GyrA)–DNA complex (GyrA–DNA complex)

Bacterial DNA gyrase is a fundamental enzyme in prokaryotes, belonging to the type II topoisomerase family, and is essential for maintaining DNA topology during replication, transcription, and recombination [UniProt: P0AES4]. It functions as an A2B2 heterotetramer, where the GyrA subunit is primarily responsible for the DNA breakage-reunion cycle [PMID: 20537116]. The GyrA subunit–DNA complex is the primary target for the fluoroquinolone class of antibiotics, such as ciprofloxacin and levofloxacin [StatPearls: Fluoroquinolones]. These drugs act by intercalating into the DNA at the cleavage site and stabilizing the covalent enzyme-DNA intermediate, known as the cleavable complex [PMID: 24508281]. This stabilization prevents the re-ligation of the DNA strands, leading to the accumulation of double-strand breaks and subsequent bacterial cell death. Resistance to these drugs often arises from specific mutations within the Quinolone Resistance-Determining Region (QRDR) of the GyrA subunit, which reduce drug binding affinity [PMID: 12654733].

Other names

DNA gyrase subunit AGyrATopoisomerase II subunit AQuinolone resistance-determining regionDNA gyrase A

Inhibition of DNA ligation by stabilizing the covalent enzyme-DNA cleavage complex, leading to double-strand DNA breaks and cell death.