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Bacillus anthracis DNA gyrase is an essential type II topoisomerase responsible for managing the topological state of DNA during replication, transcription, and recombination (UniProt: Q81S91, Q81S90). It functions as an A2B2 heterotetramer, where the GyrA subunit is involved in DNA breakage and rejoining, and the GyrB subunit provides energy through ATP hydrolysis (PubMed: 12654733). By introducing negative supercoils, the enzyme relieves the torsional strain that accumulates ahead of the replication fork, making it indispensable for bacterial survival. In the context of disease, this enzyme is the primary target for treating anthrax, a severe infection caused by B. anthracis spores (CDC: Anthrax Treatment). Fluoroquinolone antibiotics, such as ciprofloxacin, bind to the gyrase-DNA complex, trapping it and causing permanent double-strand breaks that lead to rapid bacterial cell death (PubMed: 15105405). However, the emergence of resistant strains through mutations in the quinolone resistance-determining regions (QRDR) poses a significant therapeutic challenge in biodefense and clinical settings.
Inhibition of DNA gyrase activity by stabilizing the enzyme-DNA cleavage complex, preventing DNA ligation and leading to lethal double-strand breaks (PubMed: 15105405).
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