Staphylococcus aureus topoisomerase IV (Topo IV)

Staphylococcus aureus topoisomerase IV is a type II topoisomerase enzyme essential for bacterial DNA replication and chromosome segregation (UniProt P0C1S8). It functions primarily by decatenating daughter chromosomes, allowing them to separate into new cells after replication (PubMed: 10516753). The enzyme is a heterotetramer consisting of two ParC (also known as GrlA) and two ParE (also known as GrlB) subunits. In Gram-positive bacteria like S. aureus, topoisomerase IV is the primary target for many fluoroquinolone antibiotics, such as ciprofloxacin and moxifloxacin (StatPearls: Fluoroquinolones). These drugs work by trapping the enzyme in a covalent complex with DNA, leading to permanent double-strand breaks that halt DNA synthesis and trigger bacterial cell death. Resistance to these drugs often arises from specific mutations within the enzyme's subunits, particularly in the quinolone-resistance determining regions (QRDR). Understanding the structure and function of this enzyme is vital for developing new antibiotics that can overcome existing resistance mechanisms in clinical settings.

Other names

DNA topoisomerase 4GrlA/GrlB complexParC/ParE complexTopoisomerase 4Staphylococcus aureus DNA topoisomerase IV

Inhibition of DNA decatenation by stabilizing the enzyme-DNA covalent complex (cleavable complex), leading to double-strand breaks and bacterial cell death (PubMed: 10516753).