Bacterial topoisomerase IV subunit A (ParC) (ParC)

Bacterial topoisomerase IV is an essential Type II topoisomerase responsible for the decatenation of interlinked daughter chromosomes following DNA replication (UniProt: P0A8G0). It is a heterotetrameric enzyme composed of two ParC and two ParE subunits, where the ParC subunit is primarily responsible for DNA binding and cleavage (PubMed: 12678681). The ParC subunit–DNA complex represents the transient state where the enzyme is covalently linked to the DNA backbone during the catalytic cycle. This complex is the primary target for fluoroquinolone antibiotics, which stabilize the "cleavable complex," preventing DNA religation and inducing lethal double-strand breaks (StatPearls: NBK549903). Because topoisomerase IV is distinct from eukaryotic Type II topoisomerases, it provides a basis for selective toxicity in treating bacterial infections. However, the emergence of resistance through mutations in the quinolone resistance-determining region (QRDR) of ParC remains a significant clinical challenge (PubMed: 10516753).

Other names

DNA topoisomerase 4 subunit ATopoisomerase IV subunit AParCTopo IV subunit AGyrA-like subunit of topoisomerase IV

Inhibition of DNA decatenation by stabilizing the covalent enzyme-DNA complex (cleavable complex), leading to double-strand breaks and bacterial cell death.