DNA topoisomerase 4 subunit A (ParC) (ParC)

DNA topoisomerase 4 subunit A (ParC) is a vital bacterial enzyme that plays a central role in managing DNA supercoiling and chromosome segregation during replication (UniProt: P0AFI2). It functions as part of a heterotetrameric A2B2 complex with subunit B (ParE), specifically providing the catalytic activity required for DNA decatenation—the separation of interlinked daughter chromosomes following DNA synthesis (PubMed: 12654747). This process is essential for bacterial cell division, as failure to decatenate DNA leads to cell death. ParC is a primary therapeutic target for fluoroquinolone antibiotics, particularly in Gram-positive bacteria like Staphylococcus aureus and Streptococcus pneumoniae (StatPearls: Fluoroquinolones). These drugs trap the enzyme on DNA in a cleaved state, resulting in permanent double-strand breaks that trigger bacterial cell death. Resistance to these antibiotics is a major clinical concern and is frequently mediated by point mutations in the Quinolone Resistance-Determining Region (QRDR) of the ParC subunit (PubMed: 10629206).

Other names

ParCGrlATopoisomerase IV subunit ABacterial topoisomerase IV subunit ADNA topoisomerase IV subunit A

Inhibition of DNA ligation by stabilizing the enzyme-DNA covalent cleavage complex, leading to lethal double-strand DNA breaks (StatPearls: Fluoroquinolones).