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

Bacterial topoisomerase IV is an essential type II topoisomerase enzyme that plays a critical role in bacterial cell division by decatenating interlinked daughter chromosomes following DNA replication (PubMed: 15659347). The enzyme is a heterotetramer consisting of two ParC subunits, which handle DNA cleavage and ligation, and two ParE subunits, which provide energy through ATP hydrolysis (UniProt: P0AFI2, P0AFI6). The 'cleavage complex' is a transient catalytic intermediate where the enzyme creates a double-strand break in the DNA to allow the passage of another DNA duplex. This specific state is the primary therapeutic target for fluoroquinolone antibiotics, which bind to the enzyme-DNA interface and stabilize the complex (PubMed: 20533938). By preventing the religation of the DNA strands, these drugs effectively convert the enzyme into a cellular toxin that induces permanent DNA damage and rapid bacterial cell death (StatPearls: NBK547703). Topoisomerase IV is particularly important as a target in Gram-positive bacteria, though it is also a secondary target in many Gram-negative species.

Other names

DNA topoisomerase IVTopo IVParC-ParE complexType II topoisomeraseGrlA-GrlB complex

Stabilization of the covalent enzyme-DNA cleavage complex, which prevents DNA religation and leads to lethal double-strand breaks.