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DNA topoisomerase IV subunit A is one half of the heterotetrameric type II topoisomerase complex found in bacteria, typically composed of two ParC (subunit A) and two ParE (subunit B) proteins. This enzyme plays an essential role in chromosome segregation by relaxing positive supercoils and decatenating interlinked daughter chromosomes following replication. It acts by passing one double-stranded segment of DNA through another via transient double-strand breaks, using energy from ATP hydrolysis. Topoisomerase IV is distinct from but functionally related to bacterial gyrases; unlike gyrases, it does not introduce negative supercoiling but specializes in unlinking replicated chromosomes. It is a validated antibacterial drug target—quinolone antibiotics such as ciprofloxacin inhibit its activity, leading to bactericidal effects.[1][2][4]
Inhibition of the enzyme’s ability to decatenate and relax supercoiled DNA, leading to disruption of bacterial chromosome segregation and cell death; this is the mechanism by which quinolone antibiotics act on this target.[1][4]
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