Target intelligence / Profile preview

DNA gyrase subunit B (GyrB) and DNA topoisomerase 4 subunit B (ParE) (GyrB/ParE)

Target
GyrB/ParE
Molecular classification
Enzyme, Type II topoisomerase, ATPase
01

Overview

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].

Other names
GyrBParEDNA gyrase BTopoisomerase IV subunit BDNA topoisomerase IV subunit BGyrB/ParE
02

Mechanism of action

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.

03

Biological functions

DNA replicationDNA supercoilingDNA decatenationATP hydrolysisDNA transcription
04

Disease associations

Infection
05

Safety considerations

Rapid development of bacterial resistance via point mutationsPotential gastrointestinal toxicityLimited solubility of some inhibitorsPotential for cross-reactivity with human mitochondrial topoisomerases
06

Interacting drugs

Novobiocin

5 more in the full profile.

07

Biomarkers

Minimum Inhibitory Concentration (MIC)DNA supercoiling inhibition assayBacterial load reduction

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