Bactobolin A Binds to a Site on the 70S Ribosome Distinct from Previously Seen Antibiotics

The ribosome is the target of a large number of antibiotics. Here, we report a 3.4-Å-resolution crystal structure of bactobolin A bound to 70S ribosome–tRNA complex. The antibiotic binds at a previously unseen site in the 50S subunit and displaces tRNA bound at the P-site. It thus likely has a similar mechanism of action as blasticidin S despite binding to a different site. The structure also rationalizes previously identified resistance mutations.
Graphical Abstract
Highlights • The ribosome is the target of a large number of antibiotics. • Here, we report a 3.4-Å-resolution crystal structure of bactobolin A bound to 70S ribosome–tRNA complex. • The antibiotic binds at a previously unseen site in the 50S subunit and displaces tRNA bound at the P-site that inhibits translation. • The structure also rationalizes previously identified resistance mutations.