Gyrase

Gyrase, also known as DNA gyrase, is an essential enzyme that plays a critical role in the process of DNA replication, transcription, and chromosome segregation. It is a type of topoisomerase (specifically, a Type II topoisomerase) that introduces negative supercoils into DNA. This action is crucial for relieving the torsional stress that builds up ahead of the replication fork as the DNA double helix unwinds during replication and transcription. Gyrase is unique to bacteria, making it an important target for antibacterial agents.

Function

Gyrase works by cutting both strands of the DNA helix, passing another part of the double helix through the break, and then resealing the break. This process changes the topological state of the DNA, introducing negative supercoils that are vital for compacting the DNA into the confined space of the cell and for reducing the torsional strain during DNA unwinding. The ability of gyrase to introduce negative supercoils distinguishes it from other topoisomerases, which usually relax supercoils.

Structure

The enzyme is a tetramer made up of two A subunits and two B subunits (denoted as GyrA and GyrB in bacteria). The GyrA subunits are responsible for DNA cutting and rejoining, while the GyrB subunits bind and hydrolyze ATP, providing the energy required for the conformational changes needed during the supercoiling process.

Clinical Significance

Given its critical role in bacterial DNA replication and its absence in humans, gyrase is a prime target for antibacterial drugs. The most notable examples are the quinolones and fluoroquinolones, which inhibit the DNA re-ligation step of the gyrase mechanism, leading to the accumulation of DNA breaks and ultimately bacterial cell death. Resistance to these drugs, however, is a growing concern.

Resistance Mechanisms

Bacteria have developed several mechanisms to resist the effects of gyrase inhibitors, including mutations in the gyrase gene that reduce drug binding, efflux pumps that remove the drug from the cell, and protective proteins that bind to gyrase and prevent drug interaction.

Conclusion

DNA gyrase is a vital enzyme for bacterial survival, involved in crucial cellular processes such as DNA replication and transcription. Its unique function and bacterial specificity make it an ideal target for antibacterial therapy, although resistance mechanisms present challenges that need to be addressed through ongoing research and drug development.