Evidence map›Paper›PMID 26224058›Full record

ArticleNature communications2015

Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions.

Michael R Wasserman, Arto Pulk, Zhou Zhou, Roger B Altman, John C Zinder, Keith D Green, Sylvie Garneau-Tsodikova, Jamie H Doudna Cate, Scott C Blanchard

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 77 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Mechanism of read-through enhancement by aminoglycosides and mefloquine.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Article
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  11. Identifying targets to prevent aminoglycoside ototoxicity.Molecular and cellular neurosciences · 2022
    Review
  12. Review
  13. Article
  14. Article
  15. Review
  16. Engineering ofMolecules (Basel, Switzerland) · 2021
    Article
  17. Article
  18. Article
  19. Article
  20. Real-time measurements of aminoglycoside effects on protein synthesis in live cells.Proceedings of the National Academy of Sciences of the United States of America · 2021
    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

9 authors at 4 institutions in 1 country.

Michael R WassermanDepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA.
Arto Pulk1] Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA [2] Department of Chemistry, University of California at Berkeley, Berkeley, California 94720, USA.
Zhou ZhouDepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA.
Roger B AltmanDepartment of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA.
John C ZinderTri-Institutional Training Program in Chemical Biology, Weill Cornell Medical College, Rockefeller University, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Keith D GreenDepartment of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536, USA.
Sylvie Garneau-TsodikovaDepartment of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky 40536, USA.
Jamie H Doudna Cate1] Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA [2] Department of Chemistry, University of California at Berkeley, Berkeley, California 94720, USA.
Scott C Blanchard1] Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10065, USA [2] Tri-Institutional Training Program in Chemical Biology, Weill Cornell Medical College, Rockefeller University, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Cornell University · USTri-Institutional PhD Program in Chemical Biology · USUniversity of California, Berkeley · USUniversity of Kentucky · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
The Role of the Ribosome in the Accuracy of TranslationR01GM065050 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CATE, JAMIE H · 2001 to 2022
$7.4M
Imaging Protein Synthesis on the Ribosome using Single-Molecule FRETR01GM079238 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BLANCHARD, SCOTT C · 2006 to 2023
$7.0M
Novel aminoglycoside adjuvants and stand-alone agents to combat tuberculosisR01AI090048 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GARNEAU-TSODIKOVA, SYLVIE · 2011 to 2021
$4.4M
Next-generation Fluorescent Probes for Biological ResearchR01GM098859 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI BLANCHARD, SCOTT C · 2012 to 2019
$2.9M
MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering)R01GM105404 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI TAINER, JOHN A. · 2012 to 2015
$2.1M
smFRET Investigation of Aminoglycoside-induced OtotoxicityF31DC012026 · NIDCD · WEILL MEDICAL COLL OF CORNELL UNIV · PI WASSERMAN, MICHAEL R · 2011 to 2013
$126k
NCI NIH HHS P01 CA092584NIAID NIH HHS 1R01AI090048NIAID NIH HHS R01 AI090048NIDCD NIH HHS F31 DC012026NIGMS NIH HHS 1R01GM65050NIGMS NIH HHS 2R01GM079238NIGMS NIH HHS R01 GM065050NIGMS NIH HHS R01 GM079238NIGMS NIH HHS R01 GM098859NIGMS NIH HHS R01 GM105404
6 · The paper itself

Abstract

Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin-paromomycin, ribostamycin and neamine-each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6'-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6'-substituent and the drug's net positive charge. By solving the crystal structure of the paromomycin-ribosome complex, we observe specific contacts between the apical tip of H69 and the 6'-hydroxyl on paromomycin from within the drug's canonical h44-binding site. These results indicate that aminoglycoside actions must be framed in the context of bridge B2 and their regulation of subunit rotation.

Indexed as

AminoglycosidesAnti-Bacterial AgentsBinding SitesEscherichia coliEscherichia coli ProteinsFramycetinNeomycinParomomycinRibosomesRibosome Subunits, Large, BacterialRibosome Subunits, Small, BacterialRibostamycinRNA, BacterialRotationAminoglycosidesAnti-Bacterial AgentsEscherichia coli ProteinsFramycetinneamineNeomycinParomomycinRibostamycinRNA, Bacterial

Identifiers

PMID26224058
PMCPMC4522699
OpenAlexW2202200434

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.