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DNA gyrase and DNA topoisomerase IV are essential bacterial enzymes classified as type II DNA topoisomerases[4][5][8]. They manage DNA topology during replication and cell division. DNA gyrase introduces negative supercoils into DNA, relieving positive supercoiling that accumulates ahead of the replication fork; this activity is unique to bacteria and required for maintaining genome stability[7][8][10]. Topoisomerase IV primarily resolves DNA catenanes (interlinked daughter chromosomes) by decatenation after replication and can also relax positive supercoils[1][5][4][7][8]. Both enzymes are heterotetramers (GyrA/GyrB for gyrase, ParC/ParE for topoisomerase IV) with specialized domains responsible for substrate interaction and specificity[2][4][8]. They are the principal targets of fluoroquinolone antibiotics, which either inhibit their catalytic activity or generate lethal DNA strand breaks by stabilizing enzyme–DNA cleavage complexes[3][7][1]. Mutations in either enzyme (especially gyrA, parC, and grlA) lead to resistance, a major clinical challenge.
Inhibition of catalytic activity: Prevent ATP binding or block enzyme catalysis leading to functional loss Stabilization of cleavage complexes: Induce or stabilize enzyme-DNA cleavage complexes, leading to DNA strand breaks and cell death (“topoisomerase poisoning”)
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