Gyrase is an enzyme that plays a part in managing the complex structure of DNA within cells. Its primary role involves controlling DNA’s shape and preventing tangles. This is important for the DNA to function correctly and allows cellular processes to proceed without obstruction.
Gyrase and DNA Topoisomerases
Gyrase belongs to a broader group of enzymes known as topoisomerases, which regulate the topological state of DNA. These enzymes manage DNA’s coiling and uncoiling, acting like molecular mechanics for the cell’s genetic blueprint. Gyrase is classified as a Type II topoisomerase.
Gyrase’s unique ability is to introduce negative supercoils into DNA. While other topoisomerases relax supercoils or introduce positive supercoils, gyrase uses energy to actively wind DNA, creating a more compact and accessible form. This enzyme is predominantly found in bacteria, where it is a significant contributor to maintaining their DNA structure.
The Challenge of DNA Supercoiling
DNA within a cell is a long, thread-like molecule that must be highly organized to fit into a small space. This compact packaging often leads to supercoiling. Supercoiling can be either positive, where the DNA becomes overwound and tightly coiled, or negative, where it is unwound and coiled in the opposite direction.
During cellular activities like DNA replication and transcription, DNA strands must unwind. This unwinding creates torsional stress, leading to an accumulation of positive supercoils ahead of the moving molecular machinery. If this stress is not relieved, the DNA can become tangled and impede these processes. Gyrase manages this tension.
Mechanism of Action
Gyrase functions by an intricate process involving several steps to alter DNA topology. It first binds to a segment of DNA, forming a complex that prepares the DNA for modification. The enzyme then introduces a temporary double-strand break in one section of the DNA. This break creates a gate through which another segment of the DNA molecule can pass.
After the second DNA segment has been passed through the break, gyrase reseals the broken strands, restoring the DNA’s integrity. This entire process is powered by the hydrolysis of ATP, meaning the enzyme uses energy derived from breaking down adenosine triphosphate molecules to perform its mechanical work. This energy-dependent action allows gyrase to introduce negative supercoils or relax positive supercoils.
Vital Functions in Cellular Processes
Gyrase plays a part in several cellular processes essential for the survival and propagation of organisms, especially bacteria. During DNA replication, the double helix must unwind to allow new strands to be synthesized. As the replication fork moves, it generates positive supercoils that would halt replication if not managed. Gyrase removes these positive supercoils, relieving torsional stress and allowing replication to proceed smoothly.
Similarly, in transcription, DNA unwinding also creates supercoiling. Gyrase alleviates this stress, ensuring RNA polymerase can efficiently transcribe genes. Its activity helps maintain the proper DNA structure needed for these fundamental processes. Gyrase also supports DNA repair mechanisms by ensuring the DNA remains accessible and untangled for repair enzymes.
Gyrase as a Therapeutic Target
Because bacterial gyrase is necessary for bacterial survival and has structural differences from human topoisomerases, it serves as a target for antibacterial drugs. Inhibiting this enzyme can disrupt bacterial DNA replication and transcription, leading to bacterial death. This selective targeting allows antibiotics to combat bacterial infections without significantly harming human cells.
A notable class of antibiotics that targets gyrase is the fluoroquinolones, which include common drugs like ciprofloxacin. These drugs interfere with the gyrase mechanism, specifically by stabilizing the DNA-gyrase complex after the DNA has been cut but before it is resealed. This action prevents the bacterial DNA from being properly replicated or repaired, effectively stopping bacterial growth. The importance of gyrase as a drug target is evident in its use for treating a range of bacterial infections.