DNA topoisomerase IV (Topo IV) (Topo IV)

DNA topoisomerase IV (Topo IV) is an essential bacterial type IIA topoisomerase enzyme that plays a critical role in managing DNA topology during replication and cell division [1, 3]. It is a heterotetrameric complex composed of two Subunit A (ParC in Gram-negative bacteria, GrlA in Gram-positive) and two Subunit B (ParE in Gram-negative, GrlB in Gram-positive) proteins [2, 4]. The primary biological function of Topo IV is the decatenation of interlinked daughter chromosomes following DNA replication, which is necessary for proper chromosome segregation into daughter cells [5, 9]. It also assists DNA gyrase in relaxing positive supercoils that accumulate ahead of the replication machinery [3, 18]. Topo IV is a major therapeutic target for fluoroquinolone antibiotics, such as ciprofloxacin, which act by trapping the enzyme in a covalent complex with DNA, leading to permanent double-strand breaks and rapid bacterial death [10, 12, 22]. Resistance to these agents commonly arises through specific mutations in the drug-binding regions of the ParC and ParE subunits, which reduce the affinity of the drug for the enzyme-DNA complex [13, 19].

Other names

Topoisomerase IVTopo IVParC/ParE complexGrlA/GrlB complexDNA topoisomerase 4Bacterial DNA topoisomerase IV

Fluoroquinolones like ciprofloxacin inhibit DNA topoisomerase IV by stabilizing the enzyme-DNA cleavage complex, which prevents the religation of DNA strands and leads to the formation of lethal double-strand breaks [3, 10, 12]. This poisoning of the enzyme effectively halts DNA replication and transcription, ultimately resulting in bacterial cell death [13, 20].