Revealing How GE81112 Inhibits Bacterial Protein Synthesis
A recent study by CIC bioGUNE, together with several international research institutions, investigates how the antibiotic GE81112 inhibits bacterial protein synthesis by targeting translation initiation - the earliest and rate‑limiting step¹ that allows bacteria to correctly read genetic instructions and begin making the proteins required for growth and survival.
Using high‑resolution cryo‑electron microscopy (cryo‑EM) at Diamond, the researchers visualised GE81112 bound to intact bacterial ribosomes, capturing the complex in multiple functional states that are difficult to access using other techniques.
Cryo‑EM was essential because translation initiation involves dynamic, transient conformational changes that cannot be reliably resolved by methods such as X‑ray crystallography or biochemical assays alone.
By revealing a previously unexploited ribosomal binding site and inhibitory mechanism, this work provides a structural foundation for developing new antibiotics that target translation initiation and help address antimicrobial resistance.