Escherichia coli DNA topoisomerase 4 (Topo IV)

Escherichia coli DNA topoisomerase 4 (Topo IV) is an essential bacterial type II topoisomerase enzyme responsible for the decatenation of daughter chromosomes during DNA replication [UniProt: P0AEY3, P0AEY8]. It is a heterotetrameric protein composed of two ParC and two ParE subunits, which work together to pass one double-stranded DNA molecule through another via a transient double-strand break [PubMed: 10629353]. While DNA gyrase primarily handles the introduction of negative supercoils, Topo IV is the principal enzyme for unlinking catenated chromosomes, making it indispensable for proper chromosome segregation and cell division [PubMed: 15522477]. In clinical medicine, Topo IV is a major therapeutic target for fluoroquinolone antibiotics used to treat infections caused by E. coli, including urinary tract infections and bacteremia [StatPearls: NBK547665]. These drugs exert their antibacterial effect by trapping the enzyme in a covalent complex with DNA, resulting in permanent double-strand breaks that trigger bacterial cell death [PubMed: 24563074]. However, the emergence of resistance through specific mutations in the Quinolone Resistance-Determining Regions (QRDR) of the ParC and ParE subunits remains a significant challenge in infectious disease management [PubMed: 9145820].

Other names

DNA topoisomerase IVTopoisomerase 4ParC-ParE complexDNA topoisomerase IV subunit A (ParC)DNA topoisomerase IV subunit B (ParE)

Fluoroquinolones and related antibiotics bind to the Topoisomerase IV-DNA complex, stabilizing the covalent cleavable complex where the DNA is broken but not yet religated; this prevents the completion of the catalytic cycle and leads to the accumulation of double-strand breaks, which induces the SOS response and results in bacterial cell death [PubMed: 24563074, PubMed: 12644347].