A steric block in translation caused by the antibiotic spectinomycin.
The widely used antibiotic spectinomycin inhibits bacterial protein synthesis by blocking translocation of messenger RNA and transfer RNAs on the ribosome. Here, we show that in crystals of the Escherichia coli 70S ribosome spectinomycin binding traps a distinct swiveling state of the head domain of the small ribosomal subunit. Spectinomycin also alters the rate and completeness of reverse translocation in vitro. These structural and biochemical data indicate that in solution spectinomycin sterically blocks swiveling of the head domain of the small ribosomal subunit and thereby disrupts the translocation cycle.
Borovinskaya
Maria A
MA
Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
Shoji
Shinichiro
S
Department of Microbiology, The Ohio State University, Columbus, Ohio 43210.
Holton
James M
JM
Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720.|Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158.
Fredrick
Kurt
K
Department of Microbiology, The Ohio State University, Columbus, Ohio 43210.|Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio 43210.
Cate
Jamie H D
JHD
Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720.|Department of Chemistry, University of California, Berkeley, California 94720.|Department of Molecular and Cell Biology, University of California, Berkeley, California 94720.
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli; D008968:Molecular Conformation; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000502:physiology; D017433:Protein Structure, Secondary / Q000187:drug effects / Q000502:physiology; D012329:RNA, Bacterial / Q000737:chemistry / Q000378:metabolism; D012335:RNA, Ribosomal / Q000737:chemistry / Q000378:metabolism; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism; D000198:Spectinomycin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D012329:RNA, Bacterial; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D000198:Spectinomycin
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