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The target name provided is technically inaccurate as GyrB is the B-subunit of DNA gyrase, while the corresponding B-subunit of topoisomerase IV is named ParE [1]. However, these two subunits are homologous and are frequently targeted simultaneously by the same classes of antibacterial agents due to their conserved ATP-binding domains [2]. DNA gyrase and topoisomerase IV are essential bacterial enzymes belonging to the type II topoisomerase family, responsible for managing DNA topology during replication and transcription [3]. DNA gyrase introduces negative supercoils into DNA, while topoisomerase IV primarily functions to decatenate daughter chromosomes [4]. Inhibitors such as the aminocoumarin novobiocin and the novel spiropyrimidinetrione zoliflodacin bind to the GyrB/ParE subunits to block ATP binding, effectively halting DNA replication [5]. This mechanism of action is distinct from that of fluoroquinolones, which primarily target the GyrA and ParC subunits, making GyrB/ParE inhibitors valuable against multi-drug resistant bacterial strains [6].
Inhibition of the ATPase activity of the GyrB and ParE subunits, which prevents the energy-dependent strand passage required for DNA supercoiling and decatenation, ultimately leading to the inhibition of bacterial DNA synthesis.
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