DNA topoisomerase 4 (Topo IV) (Topo IV)

DNA topoisomerase 4 (Topo IV) is an essential type II topoisomerase in Escherichia coli, composed of the ParC and ParE subunits (UniProt: P0AEY3, P0AEY8). Its primary biological function is the decatenation of daughter chromosomes following DNA replication, a process required for successful cell division and chromosome segregation (PubMed: 11029127). Unlike DNA gyrase, which primarily introduces negative supercoils, Topo IV is the principal enzyme responsible for unlinking catenated DNA circles (Nature Reviews Microbiology: doi:10.1038/nrmicro2091). In clinical medicine, Topo IV is a major target for fluoroquinolone antibiotics, such as ciprofloxacin and levofloxacin, which are used to treat infections caused by E. coli, including urinary tract infections and neonatal meningitis (StatPearls: NBK547740). These drugs act by trapping the enzyme in a covalent complex with DNA, preventing the re-ligation of double-strand breaks and leading to bacterial cell death (PubChem: CID 2764). However, the efficacy of these treatments is often limited by the development of resistance through specific mutations in the parC and parE genes (PubMed: 12654733). Furthermore, drugs targeting Topo IV are associated with significant safety concerns, including tendon rupture and central nervous system toxicity (FDA: Drug Safety Communication 2016).

Other names

Topoisomerase IVParC-ParE complexDNA topoisomerase (ATP-hydrolysing)Type II topoisomeraseTopo IVBacterial topoisomerase IVEscherichia coli topoisomerase IV

Inhibition of DNA re-ligation by stabilizing the covalent enzyme-DNA cleavage complex, leading to lethal double-strand DNA breaks (PubChem: CID 2764).