New Ribosomal Target for Antibiotic Drug Discovery

Many antibiotic agents target bacterial protein synthesis. The majority of these compounds inhibit translation by targeting functional centers in the ribosome. Only a few target sites have been identified on the ribosome.

Using single molecule fluorescence resonance energy transfer (smFRET) techniques, the inventors found crystallization conditions that favored a previously unknown, intermediate conformational state of the ribosome. They then determined the structure of the ribosome in that conformation at a high resolution (~3.2 ??). The structure reveals a neomycin -binding pocket on the ribosome, termed the H69 neomycin-binding site. This discovery provides a novel target site for antibiotic drug discovery.

This invention also provides methods of identifying candidate molecules that bind in the neomycin binding pocket and methods of testing whether the identified molecules are capable of modulating ribosomal activity.

Potential Applications

Antibiotic drug discovery