DNA gyrase–DNA cleavage complex (Streptococcus pneumoniae) (Gyrase-DNA complex)

DNA gyrase in Streptococcus pneumoniae is an essential type II topoisomerase that manages DNA topology by introducing negative supercoils, which is vital for replication and transcription (Source: UniProt P0A4G2). The DNA gyrase–DNA cleavage complex is a transient intermediate in this process, where the enzyme subunits (GyrA and GyrB) are covalently linked to the 5' ends of a cleaved DNA gate-segment. This complex is the primary pharmacological target for fluoroquinolone antibiotics, such as levofloxacin and moxifloxacin (Source: PubMed: 12654730). These drugs act as topoisomerase poisons by binding to the interface of the enzyme and DNA, effectively trapping the cleavage complex and preventing DNA re-ligation. The resulting accumulation of stabilized breaks triggers the bacterial SOS response and leads to rapid cell death (Source: StatPearls: NBK547703). Clinical resistance in S. pneumoniae frequently arises from specific mutations within the Quinolone Resistance-Determining Regions (QRDR) of the gyrase subunits, which reduce drug binding affinity to the complex.

Other names

DNA gyrase-DNA complexTopoisomerase II-DNA cleavage complexGyrase-DNA covalent complexGyrase-DNA binary complex

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