Gosset Bacterial DNA Gyrase Overview
Bacterial DNA gyrase is an essential enzyme found in all bacteria but absent from higher eukaryotes, making it a prime target for antibacterial drugs. It belongs to the type II topoisomerases and is unique among them for its ability to introduce negative supercoils into double-stranded closed-circular DNA using energy derived from ATP hydrolysis. It is a heterotetramer composed of two GyrA and two GyrB subunits (A₂B₂). Gyrase maintains homeostatic regulation of global chromosome supercoiling, allowing rapid adaptation to environmental changes. Inhibition leads to disruption in vital processes like replication and transcription, resulting in cell death or stasis.
Mechanism of Action
Fluoroquinolones stabilize the cleavage complex between gyrase and DNA, leading to double-strand breaks. Aminocoumarins inhibit ATP binding/hydrolysis. Pyrrolamides bind at the ATP pocket on GyrB.
Biological Functions
Disease Associations
Safety Considerations
- Resistance development