Bacterial DNA topoisomerase IV–DNA cleavage complex (Topo IV–DNA complex)

Bacterial DNA topoisomerase IV is a heterotetrameric type IIA topoisomerase, typically composed of two ParC and two ParE subunits, that is essential for bacterial cell division and genome stability (Source: Wikipedia, NIH). Its primary biological function is the decatenation of interlinked daughter chromosomes following DNA replication, which it achieves by creating a transient double-strand break in one DNA duplex and passing another duplex through the gate (Source: NIH, ResearchGate). The 'cleavage complex' refers to the specific intermediate state where the enzyme is covalently linked to the broken DNA strands via a phosphotyrosine bond (Source: NIH). This complex is the primary therapeutic target for fluoroquinolone antibiotics, which act as 'topoisomerase poisons' by stabilizing the complex and preventing the religation of the DNA (Source: NIH, ACS). The resulting persistence of double-strand breaks stalls replication forks and transcription machinery, triggering the bacterial SOS response and leading to rapid, irreversible cell death (Source: ResearchGate). While topoisomerase IV is a target in both Gram-positive and Gram-negative bacteria, it is often the primary target in Gram-positive species like Staphylococcus aureus and Streptococcus pneumoniae (Source: NIH, OUP).

Other names

Topoisomerase IVDNA topoisomerase 4ParC-ParE complexBacterial type IIA topoisomeraseGrlA-GrlB complex

Fluoroquinolones and other topoisomerase inhibitors bind to the interface of the topoisomerase IV–DNA complex, stabilizing the covalent enzyme-DNA intermediate (cleavage complex). This prevents the religation of the DNA strands and leads to the accumulation of lethal double-strand breaks (Source: NIH, ResearchGate).