In a new study, scientists from our top-rated Biosciences department joined forces with researchers from Jagiellonian University (Poland), and the John Innes Centre to reveal how a bacterial enzyme called DNA gyrase twists and stabilises DNA.
This discovery may pave the way for designing advanced antibiotics.
Capturing key movements of DNA gyrase
DNA gyrase, found in all bacteria but absent in humans, plays a crucial role in organising bacterial DNA, making it an ideal antibiotic target.
While the enzyme has been studied for decades, researchers were previously unable to capture the specific mechanics of its twisting motion, known as 'supercoiling.'
This is like winding an elastic band: as it twists, it coils tighter and tighter. Unlike a band that would unwind if released, DNA gyrase stabilises DNA's twisted form, making it functional for bacteria.
Using high-resolution cryo-electron microscopy, the team obtained a detailed snapshot of DNA gyrase in action, showing how it uses protein arms to wrap DNA into a 'figure-of-eight' shape.
This structure allows the enzyme to precisely break and pass sections of DNA through one another, creating stable twists.
The study reveals how gyrase functions as a molecular machine, managing each movement in a precise sequence to supercoil DNA.
A new approach to combat antibiotic resistance
DNA gyrase is already targeted by fluoroquinolone antibiotics, which prevent the enzyme from resealing DNA, effectively killing bacteria.
However, resistance to these drugs has become a widespread problem. With this clearer understanding of gyrase's structure and function, researchers can develop new antibiotics that may avoid current resistance mechanisms.
The team plans to capture additional images of gyrase in different stages of action, creating a molecular movie of the enzyme at work, which could offer precise blueprints for future antibiotic development.
This collaboration offers fresh hope in the global fight against antibiotic-resistant infections, advancing science's ability to target bacteria effectively.
