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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# Bacterial DNA gyrase (target of fluoroquinolones)

DNA gyrase is a bacteria-only topoisomerase II that introduces negative supercoils; fluoroquinolones block it.

Updated 2026-11-01

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## Key facts

- A₂B₂ tetramer: GyrA cuts and rejoins DNA (active-site tyrosine); GyrB hydrolyses ATP.
- It is the only topoisomerase that introduces negative supercoiling; it relieves the strain ahead of the fork.
- Topoisomerase IV (ParC, ParE) unlinks daughter chromosomes at the end of replication.
- Fluoroquinolones trap the cut gyrase–DNA complex (and topo IV) → double-strand breaks → bacterial death.
- In Gram-negatives the main target is usually gyrase; in Gram-positives, topo IV.

**Also called**
Bacterial topoisomerase II, Topoisomerase IV

**EC number**
[5.6.2.2](https://www.enzyme-database.org/query.php?ec=5.6.2.2)

**Genes**
gyrA, gyrB (topo IV: parC, parE)

**Structure (PDB)**
[2XCT](https://www.rcsb.org/structure/2XCT)

## Regulation

- The supercoiling level controls expression of gyrase itself (homeostatic feedback).
- Human cells have no gyrase, so the drug is selective, although high concentrations affect human topo II slightly.

## Inhibitors and toxins

- Fluoroquinolones: ciprofloxacin, levofloxacin, moxifloxacin
- Older quinolones: nalidixic acid
- Aminocoumarins (novobiocin; GyrB ATP site)

## Clinical notes

- Fluoroquinolone resistance arises mainly from mutations in the 'quinolone resistance-determining region' of gyrA and parC, and from efflux pumps.
- In multidrug-resistant tuberculosis, fluoroquinolones are second-line drugs; gyrA resistance helps define extensively drug-resistant TB with other criteria.
- Class adverse effects: tendinopathy and Achilles tendon rupture, QT prolongation, glucose disturbances; avoided where possible in children and pregnancy.

## Related conditions

- [Urinary tract infection (acute cystitis)](https://durgical.com/en/conditions/urinary-tract-infection/)
- [Acute pyelonephritis](https://durgical.com/en/conditions/acute-pyelonephritis/)
- [Tuberculosis](https://durgical.com/en/conditions/tuberculosis/)

## Related

- [Topoisomerases (I and II)](https://durgical.com/en/biochemistry/enzymes/topoisomerases/)
- [DNA replication: the replication fork](https://durgical.com/en/biochemistry/topics/dna-replication-the-replication-fork/)
- [Central dogma of molecular biology](https://durgical.com/en/biochemistry/topics/central-dogma-of-molecular-biology/)

## Test yourself

Think of the answer, then tap the question to see it.

## What activity is unique to DNA gyrase?

It introduces negative supercoils into DNA using ATP; no human enzyme does this.

## How do fluoroquinolones kill bacteria?

They trap the cut gyrase (or topo IV)–DNA complex and create lethal double-strand breaks.

## What is the main mechanism of fluoroquinolone resistance?

Mutations in gyrA and parC that weaken drug binding, plus efflux pumps.

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Educational information, not medical advice. For any symptom, see a health professional.

Sources: [gyrA: DNA gyrase subunit A (Staphylococcus aureus)](https://www.uniprot.org/uniprotkb/P20831/entry) (UniProt, 2026); [2XCT: The twinned 3.35A structure of S. aureus Gyrase complex with Ciprofloxacin and DNA](https://www.rcsb.org/structure/2XCT) (RCSB Protein Data Bank, 2026); [Ciprofloxacin: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a688016.html) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.

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