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

• Published in: Journal of molecular biology 2015-02, Vol.427 (4), p.753-755
• Main Authors: Amunts, Alexey, Fiedorczuk, Karol, Truong, Thao T., Chandler, Josephine, Greenberg, E. Peter, Ramakrishnan, V.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibiotic; Benzopyrans - chemistry; Benzopyrans - pharmacology; Brevia; Burkholderia - enzymology; Crystallography, X-Ray; Multiprotein Complexes - ultrastructure; Nucleosides - pharmacology; P-site; Ribosome Subunits, Large, Bacterial - chemistry; RNA, Transfer - metabolism; RNA, Transfer - ultrastructure; Thermus thermophilus; translation; tRNA
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2014.12.018

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. [Display omitted] •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.