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DNA gyrase and DNA topoisomerase IV (None commonly used for the pair; individual abbreviations are DNA gyrase (Gyr) and DNA topoisomerase IV (Topo IV))

Target
None commonly used for the pair; individual abbreviations are DNA gyrase (Gyr) and DNA topoisomerase IV (Topo IV)
Molecular classification
Enzyme, Type II DNA topoisomerase
01

Overview

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.

Other names
GyraseType II topoisomerase (bacterial)GyrAGyrBTopo IVParCParEType II topoisomerase IV
02

Mechanism of action

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”)

03

Biological functions

Regulation of DNA supercoilingChromosome segregationDNA replicationDecatenation (untangling of DNA)Relaxation of supercoils
04

Disease associations

Infection (specifically bacterial infection; enzymes are bacterial targets)Other (no direct role in cancer, neurodegeneration, or cardiovascular disease)
05

Safety considerations

Selective toxicity: Targeting bacterial enzymes to avoid host toxicity; human topoisomerases share structural similarity, but most drugs have high selectivityResistance development: Bacterial mutations (gyrA, grlA, parC, parE subunits) lead to reduced drug sensitivityCollateral DNA damage: Off-target effects can theoretically cause DNA damage or toxicity if selectivity is compromised
06

Interacting drugs

Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, gatifloxacin, gemifloxacin)

2 more in the full profile.

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