Structural analysis of kasugamycin inhibition of translation.
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).
Schuwirth
Barbara S
BS
Departments of Molecular and Cell Biology and Chemistry, University of California, Berkeley, California 94720, USA.
Day
J Michael
JM
Hau
Cathy W
CW
Janssen
Gary R
GR
Dahlberg
Albert E
AE
Cate
Jamie H Doudna
JH
Vila-Sanjurjo
Antón
A
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
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012333:RNA, Messenger; C100305:kasugamycin