DNA gyrase subunit A (Mycobacterium tuberculosis) (GyrA)

DNA gyrase subunit A (GyrA) is an essential component of the heterotetrameric DNA gyrase enzyme (A2B2) in Mycobacterium tuberculosis, the causative agent of tuberculosis (UniProt P9WG47). In this organism, DNA gyrase is the sole type II topoisomerase, performing the critical functions of both introducing negative supercoils and decatenating DNA during replication and transcription (PubMed 24907388). GyrA contains the breakage-reunion active site, which facilitates the transient cleavage and religation of double-stranded DNA (PubMed 17970226). This subunit is the primary target for fluoroquinolone antibiotics, such as moxifloxacin and levofloxacin, which are vital second-line treatments for tuberculosis (PubMed 20805881). These drugs act by stabilizing the covalent enzyme-DNA cleavage complex, preventing DNA repair and leading to lethal chromosomal fragmentation (PubMed 11073887). The clinical effectiveness of fluoroquinolones is frequently compromised by mutations in the gyrA gene, particularly within the quinolone resistance-determining region (QRDR) (PubMed 20805881). These mutations, such as A90V and D94G, alter the drug-binding pocket and are key biomarkers for identifying drug-resistant tuberculosis strains (PubMed 24907388). Consequently, GyrA remains a focal point for the development of novel antitubercular agents designed to overcome existing resistance mechanisms (PubMed 17970226).

Other names

GyrADNA gyrase ADNA topoisomerase 2 subunit ATopoisomerase II subunit A

Fluoroquinolones inhibit DNA gyrase by stabilizing the enzyme-DNA cleavage complex, which prevents DNA religation and leads to the accumulation of double-stranded DNA breaks, ultimately causing bacterial cell death (PubMed 17970226, 11073887, 24907388).