DNA topoisomerase 4 subunit B (ParE) (ParE)

DNA topoisomerase IV is an essential bacterial enzyme that plays a critical role in managing DNA supercoiling and unlinking intertwined daughter chromosomes (decatenation) during DNA replication (UniProt P0A7G6; PMID: 9293187). It is a heterotetrameric Type II topoisomerase consisting of two ParC subunits and two ParE subunits. The ParE subunit (also known as subunit B) contains the ATP-binding domain and provides the energy required for the enzyme's catalytic cycle through ATP hydrolysis (UniProt P0A7G6; PMID: 24597508). This enzyme is a primary target for the fluoroquinolone class of antibiotics, which interfere with the DNA ligation step, resulting in the accumulation of double-strand DNA breaks and subsequent bacterial cell death (PMID: 9371354; PMID: 24597508). Resistance to these antibiotics frequently arises through specific mutations in the ParE or ParC subunits that reduce drug binding affinity (PMID: 24597508). Topoisomerase IV is distinct from DNA gyrase, although both are Type II topoisomerases and share structural and functional similarities (PMID: 9293187).

Other names

DNA topoisomerase IV subunit BParEGrlBDNA topoisomerase IV subunit EATP-dependent DNA topoisomerase IV subunit B

Fluoroquinolones stabilize the covalent enzyme-DNA cleavage complex, preventing DNA religation and causing double-strand breaks (PMID: 9293187, 24597508). Aminocoumarins inhibit the ATPase activity of the ParE subunit by competing with ATP binding (PMID: 9293187).