Topoisomerase IV-DNA cleavage-ligation complex (Topo IV-DNA complex) (Topo IV-DNA complex)

Topoisomerase IV is a vital bacterial type II topoisomerase composed of ParC and ParE subunits, functioning as a heterotetramer (ParC2ParE2) (UniProt P0AFI2, P0AFI6). Its primary biological role is the decatenation of interlinked daughter chromosomes following DNA replication, a process essential for proper chromosome segregation during cell division (PubMed: 15139855). The enzyme operates by creating a transient double-strand break in a gate DNA segment (G-segment), passing a transport DNA segment (T-segment) through the gap, and subsequently re-ligating the break (PubMed: 21115321). This enzyme-DNA intermediate is the primary target for fluoroquinolone antibiotics, which bind to the complex and trap it in the cleaved state (StatPearls: NBK547740). By preventing the re-ligation of DNA, these drugs cause the accumulation of lethal double-strand breaks, leading to genomic instability and bacterial cell death (PubMed: 12644342).

Other names

DNA topoisomerase IV complexParC-ParE-DNA complexTopoisomerase IV-DNA binary complexQuinolone-Topoisomerase IV-DNA complexTopoisomerase IV-DNA cleavable complex

Fluoroquinolones stabilize the covalent Topoisomerase IV-DNA cleavage complex by binding at the DNA-protein interface, specifically blocking the re-ligation of the DNA strands (PubMed: 21115321). This conversion of an essential enzyme into a cellular toxin leads to the formation of permanent double-strand breaks, which triggers the bacterial SOS response and results in rapid cell death (StatPearls: NBK547740).