GyrA2GyrB2

GyrA2GyrB2 refers to the functional form of bacterial DNA gyrase, a type II topoisomerase composed of two GyrA and two GyrB subunits (A2B2). This heterotetrameric enzyme is essential for introducing negative supercoils into circular DNA, a process that facilitates DNA replication, transcription, and chromosome organization in most bacteria.

GyrA provides the DNA cleavage/religation activity through a conserved active-site tyrosine and contains a breakage-reunion domain at the N-terminus, along with a C-terminal domain that contributes to DNA wrapping and substrate interaction. GyrB contains the N-terminal ATPase domain that hydrolyzes ATP to power the catalytic cycle and a C-terminal region that supports ATPase regulation and substrate recognition. The coordinated action of GyrA and GyrB enables the strand passage mechanism that generates negative supercoiling.

Mechanistically, the enzyme binds a segment of DNA, introduces a controlled double-strand break, passes another DNA segment through the break, and reseals the DNA, using ATP hydrolysis to drive conformational changes. This process converts relaxed DNA into negatively supercoiled DNA, which is crucial for chromosome compaction and proper function of genetic processes.

Genetics and regulation typically involve gyrA and gyrB genes, which are encoded separately and often coexpressed. Expression can respond to cellular supercoiling status and environmental stresses, and proper assembly of the GyrA2GyrB2 complex is required for catalytic activity. Clinically, DNA gyrase is a primary target of fluoroquinolone antibiotics; resistance frequently arises from mutations in gyrA or gyrB, particularly within the quinolone resistance-determining region of GyrA.