DNA gyrase is an enzyme found in bacteria and some archaea, playing a unique role in their cellular processes. It belongs to a specialized group of enzymes known as type II topoisomerases. This enzyme is essential for the proper management and survival of bacterial cells, particularly in maintaining the structural integrity of their genetic material.
The DNA Supercoiling Challenge
Bacterial DNA is a long, circular molecule packed tightly within the cell. During cellular activities like DNA replication and transcription, the DNA double helix must unwind. As the DNA strands separate, this unwinding creates a twisting force, similar to twisting a rubber band or a telephone cord excessively. This over-twisting is known as “positive supercoiling” and builds up ahead of the moving molecular machinery.
This torsional strain would impede the progression of the replication fork, the site where DNA is actively being copied. If not relieved, this accumulated strain would halt DNA replication and transcription, preventing bacterial cell division and other functions.
Gyrase as a Solution
DNA gyrase directly addresses the problem of torsional strain by introducing “negative supercoils” into the bacterial DNA. It twists the DNA in the opposite direction of the natural helix, effectively under-winding it. This action counteracts the positive supercoiling that accumulates during processes like replication and transcription, thereby relieving the strain.
By introducing these negative supercoils, DNA gyrase makes the DNA more accessible for other enzymes. This allows the DNA strands to separate and unwind more easily, facilitating DNA replication and transcription.
How DNA Gyrase Works
DNA gyrase operates as a tetrameric enzyme, composed of two GyrA subunits and two GyrB subunits. The enzyme first binds to a segment of the DNA molecule.
Energy comes from adenosine triphosphate (ATP), with the GyrB subunits binding and hydrolyzing ATP. Following ATP binding, the enzyme creates a temporary break in both strands of one DNA segment, known as the “gate” or G-segment.
Through this opening, another segment of DNA, the “transfer” or T-segment, is passed. After the T-segment moves through the break, the enzyme reseals the DNA break. This process changes the DNA’s linking number by two, introducing two negative supercoils with each cycle.
Targeting DNA Gyrase in Medicine
DNA gyrase holds significant practical importance for human health because, while it is present and indispensable in bacteria, it is absent from human cells. Human cells utilize different types of topoisomerases to manage their DNA topology.
This difference makes bacterial DNA gyrase a selective target for antibacterial medications. Quinolones, a class of antibiotics including ciprofloxacin, specifically target this enzyme.
These antibiotics work by inhibiting DNA gyrase by stabilizing its complex with DNA after it makes a double-strand break. This stabilization prevents the enzyme from resealing the DNA, stalling bacterial DNA replication and transcription. This disruption ultimately leads to bacterial cell death.