Evidence map›Paper›PMID 24961372›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Macrolide antibiotics allosterically predispose the ribosome for translation arrest.

Shanmugapriya Sothiselvam, Bo Liu, Wei Han, Haripriya Ramu, Dorota Klepacki, Gemma Catherine Atkinson, Age Brauer, Maido Remm, Tanel Tenson, Klaus Schulten and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

65 citing papers in PubMed, 115 citations in OpenAlex.

  1. Approaches for Studying Context Specificity of Translation Inhibitor Action.International journal of molecular sciences · 2026
    Review
  2. Article
  3. RiboScreenBiomedicines · 2026
    Review
  4. Article
  5. Article
  6. The Crisis of Macrolide Resistance in Pneumococci in Latin America.The American journal of tropical medicine and hygiene · 2024
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Machines on Genes through the Computational Microscope.Journal of chemical theory and computation · 2023
    Review
  13. Article
  14. Article
  15. Cryo-EM structure ofEmerging microbes & infections · 2022
    Article
  16. Article
  17. Article
  18. Review
  19. The Peptidyl Transferase Center: a Window to the Past.Microbiology and molecular biology reviews : MMBR · 2021
    Article
  20. Article

5 more citing papers are in PubMed but not listed here.

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

12 authors at 3 institutions in 3 countries.

Shanmugapriya SothiselvamCenter for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607;
Bo LiuBeckman Institute and Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
Wei HanBeckman Institute and Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
Haripriya RamuCenter for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607;
Dorota KlepackiCenter for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607;
Gemma Catherine AtkinsonInstitute of Technology, University of Tartu, 50411 Tartu, Estonia;Department of Molecular Biology andLaboratory for Molecular Infection Medicine Sweden, Umeå University, Umeå 90187, Sweden; and.
Age BrauerInstitute of Molecular and Cell Biology, University of Tartu, 50411 Tartu, Estonia.
Maido RemmInstitute of Molecular and Cell Biology, University of Tartu, 50411 Tartu, Estonia.
Tanel TensonInstitute of Technology, University of Tartu, 50411 Tartu, Estonia;
Klaus SchultenBeckman Institute and Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801;
Nora Vázquez-LaslopCenter for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607; shura@uic.edu nvazquez@uic.edu.
Alexander S MankinCenter for Pharmaceutical Biotechnology, University of Illinois, Chicago, IL 60607; shura@uic.edu nvazquez@uic.edu.
University of Illinois Chicago · USUniversity of Tartu · EEUniversity of Illinois Urbana-Champaign · US

Funding

WHOLE CELL SIMULATIONP41GM104601 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI TAJKHORSHID, EMAD · 2012 to 2021
$19.0M
Programmed translation arrest controlled by nascent peptides and antibioticsR01GM104370 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MANKIN, ALEXANDER S, VAZQUEZ-LASLOP, NORA · 2012 to 2015
$1.2M
NIGMS NIH HHS 9P41GM104601NIGMS NIH HHS P41 GM104601NIGMS NIH HHS R01 GM104370NIGMS NIH HHS R01GM104370
6 · The paper itself

Abstract

Translation arrest directed by nascent peptides and small cofactors controls expression of important bacterial and eukaryotic genes, including antibiotic resistance genes, activated by binding of macrolide drugs to the ribosome. Previous studies suggested that specific interactions between the nascent peptide and the antibiotic in the ribosomal exit tunnel play a central role in triggering ribosome stalling. However, here we show that macrolides arrest translation of the truncated ErmDL regulatory peptide when the nascent chain is only three amino acids and therefore is too short to be juxtaposed with the antibiotic. Biochemical probing and molecular dynamics simulations of erythromycin-bound ribosomes showed that the antibiotic in the tunnel allosterically alters the properties of the catalytic center, thereby predisposing the ribosome for halting translation of specific sequences. Our findings offer a new view on the role of small cofactors in the mechanism of translation arrest and reveal an allosteric link between the tunnel and the catalytic center of the ribosome.

Indexed as

Allosteric RegulationAnti-Bacterial AgentsCell-Free SystemMacrolidesMolecular ConformationMolecular Dynamics SimulationProtein BiosynthesisRibosomesAnti-Bacterial AgentsMacrolidesazithromycinketolidessolithromycin

Identifiers

PMID24961372
PMCPMC4103360
OpenAlexW2134600600

What OpenQuestion holds

Textmetadata
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.