Target intelligence / Profile preview

Mycobacterium tuberculosis topoisomerase IV (Topo IV)

Target
Topo IV
Molecular classification
Enzyme, Type II topoisomerase
01

Overview

Mycobacterium tuberculosis topoisomerase IV is a theoretical enzyme complex that is notably absent from the Mycobacterium tuberculosis genome. In most bacteria, topoisomerase IV (composed of ParC and ParE subunits) is responsible for decatenating daughter chromosomes following DNA replication. However, Mycobacterium tuberculosis is unique among many bacteria in that it lacks the genes for topoisomerase IV and instead relies solely on DNA gyrase to perform both DNA supercoiling and decatenation functions (PMID: 15184351, 22493353). Consequently, while topoisomerase IV is a major target for fluoroquinolone antibiotics in other pathogens like Staphylococcus aureus or Escherichia coli, it is not a valid therapeutic target in M. tuberculosis. Drugs used to treat tuberculosis that target Type II topoisomerases, such as moxifloxacin or gatifloxacin, actually exert their effect by binding to the M. tuberculosis DNA gyrase (PMID: 12644283).

Other names
ParC-ParE complexType II topoisomerase
02

Mechanism of action

Inhibition of DNA strand re-ligation leading to double-strand breaks and bacterial cell death

03

Biological functions

DNA decatenationDNA relaxationChromosome segregation
04

Disease associations

Infection
05

Safety considerations

Target absence in Mycobacterium tuberculosisCross-reactivity with human topoisomerase II

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