Bacillus anthracis DNA gyrase subunit A (GyrA)

Bacillus anthracis DNA gyrase subunit A, commonly known as GyrA, is a critical enzyme component of the bacterial type IIA topoisomerase complex [1.2.5]. It functions as a heterotetramer (A2B2) alongside subunit B (GyrB) to regulate DNA topology by introducing negative supercoils, which is essential for DNA replication, transcription, and repair [1.4.4]. GyrA specifically mediates the ATP-dependent breakage and rejoining of double-stranded DNA to alleviate torsional stress ahead of the replication fork [1.3.4, 1.4.3]. In Bacillus anthracis, the causative agent of anthrax, GyrA is the primary cellular target for the quinolone class of antibiotics, such as ciprofloxacin [1.3.1]. These drugs act as topoisomerase poisons by stabilizing the covalent enzyme-DNA cleavage complex, preventing DNA religation and leading to lethal double-strand breaks and bacterial cell death [1.3.4, 1.4.4]. Resistance to these agents frequently arises from specific point mutations in the GyrA protein, particularly at residues Ser85 and Glu89, which disrupt the water-metal ion bridge necessary for drug binding [1.3.1, 1.3.3].

Other names

GyrADNA topoisomerase 2 subunit ADNA topoisomerase II subunit ADNA gyrase subunit A (Bacillus anthracis)

Quinolones act as topoisomerase poisons by stabilizing the DNA-gyrase cleavage complex, which prevents the religation of double-stranded DNA breaks and leads to bacterial cell death.