DNA topoisomerase 4 (Staphylococcus aureus) (Topo IV)

DNA topoisomerase 4 (Staphylococcus aureus), commonly known as Topoisomerase IV, is an essential type II topoisomerase enzyme composed of two subunits, GrlA and GrlB (UniProt: P0C1U8, P0C1V0). Its primary biological function is the decatenation of daughter chromosomes following DNA replication, a process necessary for successful cell division and chromosome segregation (PMID: 8659971). In addition to decatenation, it assists in the relaxation of positive DNA supercoils that accumulate ahead of the replication fork. In Staphylococcus aureus, Topoisomerase IV is a major therapeutic target for fluoroquinolone antibiotics, which act by trapping the enzyme in a covalent complex with DNA, leading to lethal double-strand breaks (PMID: 10516771). The enzyme is particularly significant in the context of methicillin-resistant Staphylococcus aureus (MRSA) infections, where it often serves as the primary target for newer quinolones. However, clinical efficacy is frequently challenged by the development of resistance mutations within the quinolone resistance-determining regions (QRDR) of the grlA and grlB genes. Understanding the structural and functional nuances of this enzyme is critical for the development of next-generation antibacterial agents designed to overcome existing resistance mechanisms (PMID: 30213815).

Other names

Topoisomerase IVGrlA/GrlB complexParC/ParE complexDNA topoisomerase IV

Inhibition of the enzyme's ability to ligate DNA after cleavage, resulting in the accumulation of double-strand DNA breaks and subsequent bacterial cell death.