Streptococcus pneumoniae topoisomerase IV (Topo IV)

Streptococcus pneumoniae topoisomerase IV is an essential bacterial type II topoisomerase composed of two subunits, ParC and ParE, which form a heterotetrameric complex. Its primary biological role is the decatenation of daughter chromosomes following DNA replication, ensuring successful chromosome segregation during cell division [1][2]. This enzyme is a major therapeutic target for fluoroquinolone antibiotics used to treat pneumococcal infections such as pneumonia, meningitis, and bacteremia [3]. Fluoroquinolones act by stabilizing the covalent enzyme-DNA cleavage complex, which prevents the religation of DNA strands and leads to lethal double-strand breaks [4][5]. Clinical challenges include the emergence of resistance, primarily driven by point mutations in the Quinolone Resistance-Determining Regions (QRDR) of the parC and parE genes [6]. Understanding the structural interactions between the enzyme and inhibitors is vital for developing next-generation antibiotics to combat resistant strains.

Other names

DNA topoisomerase 4ParC-ParE complexTopoisomerase 4

Inhibition of DNA replication by stabilizing the covalent enzyme-DNA cleavage complex, preventing DNA religation and causing lethal double-strand breaks [4][5].