Evidence map›Paper›PMID 25306922›Full record

ArticleMolecular cell2014

Negamycin interferes with decoding and translocation by simultaneous interaction with rRNA and tRNA.

Yury S Polikanov, Teresa Szal, Fuyan Jiang, Pulkit Gupta, Ryoichi Matsuda, Masataka Shiozuka, Thomas A Steitz, Nora Vázquez-Laslop, Alexander S Mankin

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

33 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Negamycin: Nature's Forgotten Antibiotic.ACS infectious diseases · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Paenilamicins from the honey bee pathogenbioRxiv : the preprint server for biology · 2024
    Article
  8. Hibernating ribosomes as drug targets?Frontiers in microbiology · 2024
    Review
  9. Article
  10. Review
  11. Article
  12. Repurposing tRNAs for nonsense suppression.Nature communications · 2021
    Article
  13. Article
  14. Nonsense suppression therapies in human genetic diseases.Cellular and molecular life sciences : CMLS · 2021
    Review
  15. Article
  16. Article
  17. Sarecycline interferes with tRNA accommodation and tethers mRNA to the 70S ribosome.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  18. Article
  19. Article
  20. Review
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

9 authors at 5 institutions in 2 countries.

Yury S PolikanovDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.
Teresa SzalCenter for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL 60607, USA.
Fuyan JiangCenter for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL 60607, USA; Adlai E. Stevenson High School, Lincolnshire, IL 60069, USA.
Pulkit GuptaCenter for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL 60607, USA.
Ryoichi MatsudaDepartment of Life Sciences, The University of Tokyo at Komaba, Komaba, 153-8902, Japan.
Masataka ShiozukaDepartment of Life Sciences, The University of Tokyo at Komaba, Komaba, 153-8902, Japan.
Thomas A SteitzDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA. Electronic address: thomas.steitz@yale.edu.
Nora Vázquez-LaslopCenter for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL 60607, USA. Electronic address: nvazquez@uic.edu.
Alexander S MankinCenter for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL 60607, USA.
University of Illinois Chicago · USHoward Hughes Medical Institute · USThe University of Tokyo · JPTokyo Metropolitan Komaba High School · JPYale University · US

Funding

X-RAY ANALYSIS OF PROTEIN STRUCTURE AND FUNCTIONP01GM022778 · NIGMS · YALE UNIVERSITY · PI BREAKER, RONALD R · 1985 to 2019
$26.1M
Molecular mechanisms of action of macrolide antibioticsR01GM106386 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI MANKIN, ALEXANDER S, VAZQUEZ-LASLOP, NORA · 2013 to 2016
$1.2M
Howard Hughes Medical InstituteNIGMS NIH HHS GM022778NIGMS NIH HHS GM106386NIGMS NIH HHS P01 GM022778NIGMS NIH HHS R01 GM106386
6 · The paper itself

Abstract

Negamycin (NEG) is a ribosome-targeting antibiotic that exhibits clinically promising activity. Its binding site and mode of action have remained unknown. We solved the structure of the Thermus thermophilus ribosome bound to mRNA and three tRNAs, in complex with NEG. The drug binds to both small and large ribosomal subunits at nine independent sites. Resistance mutations in the 16S rRNA unequivocally identified the binding site in the vicinity of the conserved helix 34 (h34) in the small subunit as the primary site of antibiotic action in the bacterial and, possibly, eukaryotic ribosome. At this site, NEG contacts 16S rRNA as well as the anticodon loop of the A-site tRNA. Although the NEG site of action overlaps with that of tetracycline (TET), the two antibiotics exhibit different activities: while TET sterically hinders binding of aminoacyl-tRNA to the ribosome, NEG stabilizes its binding, thereby inhibiting translocation and stimulating miscoding.

Indexed as

Amino Acid MotifsAmino Acids, DiaminoAnti-Bacterial AgentsBase SequenceBinding SitesCrystallography, X-RayModels, MolecularProtein BiosynthesisProtein Synthesis InhibitorsRibosome Subunits, Large, BacterialRibosome Subunits, Small, BacterialRNA, BacterialRNA, MessengerRNA, RibosomalRNA StabilityRNA, TransferAmino Acids, DiaminoAnti-Bacterial AgentsnegamycinProtein Synthesis InhibitorsRNA, BacterialRNA, MessengerRNA, RibosomalRNA, Transfer

Identifiers

PMID25306922
PMCPMC4334386
OpenAlexW2005480696

What OpenQuestion holds

Textmetadata
LicenceTDM
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.