DNA gyrase subunit A C-terminal domain (GyrA CTD)

The DNA gyrase subunit A C-terminal domain (GyrA CTD) is an essential structural and functional component of bacterial DNA gyrase, the only enzyme capable of introducing negative supercoils into DNA. It possesses a unique 'beta-pinwheel' fold that enables the enzyme to bind and wrap the DNA substrate, a critical prerequisite for the strand-passage reaction that alters DNA topology. By facilitating this wrapping, the GyrA CTD ensures the correct orientation of the G-segment and T-segment of DNA, allowing for efficient supercoiling during replication and transcription. This domain is a major focus for antibacterial drug development because its specific structural architecture is absent in eukaryotic topoisomerases, providing a high degree of therapeutic selectivity. While classic fluoroquinolones primarily target the catalytic N-terminal domain and its interface with GyrB, the CTD is a target for novel inhibitors like Simocyclinone D8, which block the initial DNA-binding and wrapping steps. Mutations within the GyrA CTD or the nearby Quinolone Resistance-Determining Region (QRDR) are primary drivers of clinical antibiotic resistance, necessitating ongoing research into this domain's structural dynamics.

Other names

GyrA-CTDDNA topoisomerase 2 subunit A C-terminal domainBeta-pinwheel domainDNA wrapping domain of GyrA

Inhibition of the DNA wrapping mechanism essential for negative supercoiling; stabilization of the covalent enzyme-DNA cleavage complex leading to double-strand breaks; prevention of DNA binding to the gyrase complex.