title: Structural analysis of kasugamycin inhibition of translation.
abstract: The prokaryotic ribosome is an important target of antibiotic action. We determined the X-ray structure of the aminoglycoside kasugamycin (Ksg) in complex with the Escherichia coli 70S ribosome at 3.5-A resolution. The structure reveals that the drug binds within the messenger RNA channel of the 30S subunit between the universally conserved G926 and A794 nucleotides in 16S ribosomal RNA, which are sites of Ksg resistance. To our surprise, Ksg resistance mutations do not inhibit binding of the drug to the ribosome. The present structural and biochemical results indicate that inhibition by Ksg and Ksg resistance are closely linked to the structure of the mRNA at the junction of the peptidyl-tRNA and exit-tRNA sites (P and E sites).
authors.affiliation: Departments of Molecular and Cell Biology and Chemistry, University of California, Berkeley, California 94720, USA.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Schuwirth
authors.forename: J Michael
authors.initials: JM
authors.lastname: Day
authors.forename: Cathy W
authors.initials: CW
authors.lastname: Hau
authors.forename: Gary R
authors.initials: GR
authors.lastname: Janssen
authors.forename: Albert E
authors.initials: AE
authors.lastname: Dahlberg
authors.forename: Jamie H Doudna
authors.initials: JH
authors.lastname: Cate
authors.forename: Antón
authors.initials: A
authors.lastname: Vila-Sanjurjo
mesh_terms: D000617:Aminoglycosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D004926:Escherichia coli / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000737:chemistry*; D012333:RNA, Messenger / Q000737:chemistry*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013698:Templates, Genetic
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012333:RNA, Messenger; C100305:kasugamycin