Staphylococcus aureus topoisomerase IV (Topo IV) (Topo IV)

Staphylococcus aureus topoisomerase IV is a type II topoisomerase essential for bacterial viability, primarily responsible for the decatenation of daughter chromosomes during DNA replication (PubMed, PMID: 10817700). The enzyme is a heterotetramer consisting of two GrlA and two GrlB subunits, which are the functional homologs of ParC and ParE in other species (UniProt, P0A0J4). It plays a pivotal role in resolving the topological knots and catenanes that form as the replication fork progresses, ensuring proper chromosome segregation into daughter cells (StatPearls, NBK547665). In S. aureus, this enzyme is a major therapeutic target for fluoroquinolone antibiotics, such as ciprofloxacin and moxifloxacin, which stabilize the enzyme-DNA cleavage complex to induce cell death (PubMed, PMID: 12654739). Resistance to these treatments is a significant clinical challenge, often mediated by point mutations in the quinolone resistance-determining regions (QRDR) of the grlA and grlB genes (PubMed, PMID: 9145860).

Other names

DNA topoisomerase 4GrlA-GrlB complexTopoisomerase 4ParC-ParE complex

Inhibition of DNA decatenation by stabilizing the covalent enzyme-DNA cleavage complex, preventing DNA religation and causing lethal double-strand breaks (PubMed, PMID: 12654739).