Bacterial DNA gyrase–DNA cleavage complex (Gyrase-DNA complex)

Bacterial DNA gyrase is an essential Type II topoisomerase responsible for introducing negative supercoils into DNA, a process critical for maintaining genomic integrity during replication and transcription (UniProt P0AES4). The DNA gyrase–DNA cleavage complex is a transient catalytic intermediate where the enzyme subunits are covalently linked to the 5' ends of a broken DNA duplex (PubMed: 24599509). This complex serves as the primary molecular target for several classes of antibiotics, most notably the fluoroquinolones (StatPearls: Fluoroquinolones). These drugs act by intercalating into the DNA at the cleavage site and stabilizing the complex, which prevents the religation of the DNA strands (PubMed: 12634337). The resulting accumulation of stabilized cleavage complexes leads to the formation of permanent double-strand breaks, triggering a SOS response and rapid bacterial cell death. Because DNA gyrase is absent in eukaryotes, it remains a high-selectivity target for treating a wide range of bacterial infections, although rising resistance through target-site mutations poses a significant clinical challenge (PubMed: 20573937). Notable safety concerns for drugs targeting this complex include tendon rupture and central nervous system toxicity (FDA Drug Safety Communication).

Other names

DNA gyrase-DNA adductGyrase-DNA binary complexTopoisomerase II-DNA cleavage complexQuinolone-gyrase-DNA complex

Stabilization of the covalent DNA gyrase-DNA cleavage complex, preventing DNA religation and inducing lethal double-strand breaks.