title: The complex of a designer antibiotic with a model aminoacyl site of the 30S ribosomal subunit revealed by X-ray crystallography.
abstract: The ribosome is an important target for aminoglycoside antibiotics; however, the clinical effectiveness of aminoglycosides has diminished due to bacterial resistance mechanisms. Here we report the X-ray structure of a novel synthetic aminoglycoside bound to the A site of the ribosome, its target for manifestation of activity. The structure validates the in silico design paradigms for the antibiotic and reveals the molecular interactions made by this novel antibiotic in prokaryotes.
authors.affiliation: RiboTargets, Granta Park, Cambridge CB1 6GB, United Kingdom.
authors.forename: Rupert J M
authors.initials: RJ
authors.lastname: Russell
authors.forename: James B
authors.initials: JB
authors.lastname: Murray
authors.forename: Georg
authors.initials: G
authors.lastname: Lentzen
authors.forename: Jalal
authors.initials: J
authors.lastname: Haddad
authors.forename: Shahriar
authors.initials: S
authors.lastname: Mobashery
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018360:Crystallography, X-Ray; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D009690:Nucleic Acid Conformation; D010303:Paromomycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012335:RNA, Ribosomal / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D012335:RNA, Ribosomal; D010303:Paromomycin