DNA gyrase (Mycobacterium tuberculosis) (DNA gyrase)

DNA gyrase is an essential type II topoisomerase in Mycobacterium tuberculosis (Mtb) that regulates DNA topology by introducing negative supercoils into the bacterial chromosome [1]. It functions as a heterotetramer consisting of two GyrA and two GyrB subunits, which are responsible for DNA breakage/reunion and ATP hydrolysis, respectively [2]. Uniquely, Mtb lacks topoisomerase IV, meaning DNA gyrase must perform both supercoiling and the decatenation of daughter chromosomes, making it indispensable for DNA replication and transcription [3]. This enzyme is the primary target for fluoroquinolone antibiotics, such as moxifloxacin and levofloxacin, which are critical components of second-line treatments for tuberculosis [4]. These drugs act by stabilizing the "cleavable complex" between the enzyme and DNA, resulting in lethal double-strand breaks [5]. Resistance is a significant clinical challenge, often driven by mutations in the Quinolone Resistance-Determining Regions (QRDR) of the gyrA and gyrB genes [6].

Other names

DNA topoisomerase IIGyrA-GyrB complexType II DNA topoisomerase

Inhibition of the DNA cleavage-religation cycle by stabilizing the covalent enzyme-DNA complex, leading to permanent double-strand breaks and inhibition of DNA synthesis.