Target intelligence / Profile preview

DNA topoisomerase IV subunit A (ParC)

Target
ParC
Molecular classification
Enzyme, Type II DNA topoisomerase[1][9], ATP-hydrolyzing enzyme[2][4]
01

Overview

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]

Other names
Topoisomerase IV subunit AparCgrlA (in some species)DNA topoisomerase 4 subunit A[2][4][6]
02

Mechanism of action

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]

03

Biological functions

Chromosome segregation during cell division[1][2][6]Relaxation of supercoiled DNA[1][2]Decatenation (unlinking) of replicated circular DNA molecules[1][2]Response to antibiotics (in bacteria)[4]
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Disease associations

Infection (as a bacterial target for antibiotics)[1]
05

Safety considerations

Development of antibiotic resistance in bacteria due to mutations in parC or related genes, reducing drug efficacy.[1]No direct human safety concerns as it is a bacterial protein.
06

Interacting drugs

Ciprofloxacin[1][4]

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