DNA gyrase subunit B (GyrB) ATPase domain (GyrB ATPase domain)

Mycobacterial DNA gyrase subunit B (GyrB) ATPase domain is a vital enzymatic component of the DNA gyrase complex, which is the only type II topoisomerase present in Mycobacterium tuberculosis (UniProt P9WG47). This domain facilitates the hydrolysis of ATP, providing the necessary energy for the enzyme to introduce negative supercoils into the bacterial genome, a process essential for DNA replication, transcription, and recombination (PubMed: 25633144). Because of its fundamental role in maintaining DNA topology, it is a validated target for the development of anti-tubercular agents. Drugs targeting this domain, such as the aminocoumarin novobiocin and the clinical candidate SPR719, function by competitively binding to the ATP pocket, thereby preventing the energy-dependent strand passage required for catalytic activity (PubMed: 30115753). This mechanism is distinct from that of fluoroquinolones, which target the GyrA subunit, making GyrB inhibitors effective against many drug-resistant strains. However, challenges in drug development include ensuring selectivity over human ATPases and managing the potential for rapid resistance development through point mutations in the GyrB gene (PubMed: 28804012).

Other names

GyrBDNA topoisomerase 2 subunit BATP-binding domain of DNA gyrase subunit BMycobacterial GyrBGyrB ATPase

Competitive inhibition of the ATP-binding site on the GyrB subunit, which prevents ATP hydrolysis and the subsequent energy-driven DNA strand passage and supercoiling necessary for bacterial DNA replication and transcription (PubMed: 25633144).