title: Bactobolin A binds to a site on the 70S ribosome distinct from previously seen antibiotics.
abstract: 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.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB20QH, UK.
authors.forename: Alexey
authors.initials: A
authors.lastname: Amunts
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB20QH, UK.
authors.forename: Karol
authors.initials: K
authors.lastname: Fiedorczuk
authors.affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Thao T
authors.initials: TT
authors.lastname: Truong
authors.affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Chandler
authors.affiliation: Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
authors.forename: E Peter
authors.initials: EP
authors.lastname: Greenberg
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge CB20QH, UK. Electronic address: ramak@mrc-lmb.cam.ac.uk.
authors.forename: V
authors.initials: V
authors.lastname: Ramakrishnan
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology; D019117:Burkholderia / Q000201:enzymology; D018360:Crystallography, X-Ray; D046912:Multiprotein Complexes / Q000648:ultrastructure; D009705:Nucleosides / Q000494:pharmacology; D012343:RNA, Transfer / Q000378:metabolism / Q000648:ultrastructure; D054681:Ribosome Subunits, Large, Bacterial / Q000737:chemistry*; D016963:Thermus thermophilus
chemical_list: D000900:Anti-Bacterial Agents; D001578:Benzopyrans; D046912:Multiprotein Complexes; D009705:Nucleosides; C025268:bactobolin; C004500:blasticidin S; D012343:RNA, Transfer
keywords: P-site; antibiotic; tRNA; translation