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PMID: 17696316 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

A steric block in translation caused by the antibiotic spectinomycin.

ACS chemical biology ·Vol. 2 ·No. 8 ·2007-08-17 ·Pages 545-552

Borovinskaya MA, Shoji S, Holton JM, Fredrick K, Cate JHD

Abstract

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.

MeSH Terms
Anti-Bacterial Agents/chemistry,metabolism,pharmacology Escherichia coli Molecular Conformation Protein Biosynthesis/drug effects,physiology Protein Structure, Secondary/drug effects,physiology RNA, Bacterial/chemistry,metabolism RNA, Ribosomal/chemistry,metabolism Ribosomal Proteins/chemistry,metabolism Spectinomycin/chemistry,metabolism,pharmacology
Chemicals
Anti-Bacterial Agents RNA, Bacterial RNA, Ribosomal Ribosomal Proteins Spectinomycin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Borovinskaya Maria A
Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720.
Shoji Shinichiro
Department of Microbiology, The Ohio State University, Columbus, Ohio 43210.
Holton James M
Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720. | Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158.
Fredrick Kurt
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
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.
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Article Info
Journal
ACS chemical biology
Abbr.
ACS Chem Biol
ISSN
1554-8937
DOI
10.1021/cb700100n
Published
2007-08-17
Epub
2007-00-10
Pages
545-552
Language
English
Region
United States
NLM ID
101282906
PMCID
PMC4624401
Subset
IM
Grants
NIGMS NIH HHS · R01 GM065050 · United States
NCI NIH HHS · CA92584 · United States
NIGMS NIH HHS · GM65050 · United States
NCI NIH HHS · P01 CA092584 · United States
NIGMS NIH HHS · R01 GM072528-04 · United States
NIGMS NIH HHS · GM072528 · United States
NIGMS NIH HHS · R01 GM072528 · United States
Databases
PDB
2QOU, 2QOV, 2QOW, 2QOX, 2QOY, 2QOZ, 2QP0, 2QP1
External Links
PubMed source DOI: 10.1021/cb700100n PMC Full Text View journal details
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