Evidence map›Paper›PMID 24412368›Full record

ArticleCell reports2014

The antibiotics dityromycin and GE82832 bind protein S12 and block EF-G-catalyzed translocation.

David Bulkley, Letizia Brandi, Yury S Polikanov, Attilio Fabbretti, Michael O'Connor, Claudio O Gualerzi, Thomas A Steitz

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
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  3. Article
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  7. Structural basis for ribosome recycling by RRF and tRNA.Nature structural & molecular biology · 2020
    Article
  8. Article
  9. Draft Genome Sequence ofMicrobiology resource announcements · 2019
    Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Review
  17. Bacterial Protein Synthesis as a Target for Antibiotic Inhibition.Cold Spring Harbor perspectives in medicine · 2016
    Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

David BulkleyDepartment of Chemistry, Yale University, New Haven, CT 06511, USA.
Letizia BrandiLaboratory of Genetics, Department of Biosciences and Biotechnology, University of Camerino, 62032 Camerino, Italy.
Yury S PolikanovDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA; Howard Hughes Medical Institute, New Haven, CT 06511, USA.
Attilio FabbrettiLaboratory of Genetics, Department of Biosciences and Biotechnology, University of Camerino, 62032 Camerino, Italy.
Michael O'ConnorSchool of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA.
Claudio O GualerziLaboratory of Genetics, Department of Biosciences and Biotechnology, University of Camerino, 62032 Camerino, Italy. Electronic address: claudio.gualerzi@unicam.it.
Thomas A SteitzDepartment of Chemistry, Yale University, New Haven, CT 06511, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA; Howard Hughes Medical Institute, New Haven, CT 06511, USA. Electronic address: thomas.steitz@yale.edu.
Università di Camerino · ITHoward Hughes Medical Institute · USUniversity of Missouri–Kansas City · USYale University · US

Funding

X-RAY ANALYSIS OF PROTEIN STRUCTURE AND FUNCTIONP01GM022778 · NIGMS · YALE UNIVERSITY · PI BREAKER, RONALD R · 1985 to 2019
$26.1M
Howard Hughes Medical InstituteNIGMS NIH HHS P01 GM022778
6 · The paper itself

Abstract

The translocation of mRNA and tRNA through the ribosome is catalyzed by elongation factor G (EF-G), a universally conserved guanosine triphosphate hydrolase (GTPase). The mechanism by which the closely related decapeptide antibiotics dityromycin and GE82832 inhibit EF-G-catalyzed translocation is elucidated in this study. Using crystallographic and biochemical experiments, we demonstrate that these antibiotics bind to ribosomal protein S12 in solution alone as well as within the small ribosomal subunit, inducing long-range effects on the ribosomal head. The crystal structure of the antibiotic in complex with the 70S ribosome reveals that the binding involves conserved amino acid residues of S12 whose mutations result in in vitro and in vivo antibiotic resistance and loss of antibiotic binding. The data also suggest that GE82832/dityromycin inhibits EF-G-catalyzed translocation by disrupting a critical contact between EF-G and S12 that is required to stabilize the posttranslocational conformation of EF-G, thereby preventing the ribosome-EF-G complex from entering a conformation productive for translocation.

Indexed as

Amino Acid SequenceAnti-Bacterial AgentsBacterial ProteinsBinding SitesEscherichia coliMolecular Docking SimulationMolecular Sequence DataPeptide Chain Elongation, TranslationalPeptide Elongation Factor 2PeptidesProtein BindingThermus thermophilusAnti-Bacterial AgentsBacterial ProteinsGE82832 peptide, Streptosporangium cinnabarinumPeptide Elongation Factor 2Peptides

Identifiers

PMID24412368
PMCPMC5331365
OpenAlexW2083279236

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.