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

• DOI: 10.1016/j.jmb.2014.12.018
• Publication Date: 2015-01-03T01:47:21Z
• Authors: Alexey Amunts; Karol Fiedorczuk; Thao T. Truong; Josephine Chandler; E. Peter Greenberg; V. Ramakrishnan
• Keywords: 0303 health sciences; Burkholderia; Thermus thermophilus; P-site; translation; Nucleosides; Ribosome Subunits, Large, Bacterial; Crystallography, X-Ray; Brevia; Anti-Bacterial Agents; 03 medical and health sciences; RNA, Transfer; antibiotic; Multiprotein Complexes; Benzopyrans; tRNA; Molecular Biology

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.