Evidence map›Paper›PMID 25233066›Full record

ArticleeLife2014

Discovery of a small molecule that inhibits bacterial ribosome biogenesis.

Jonathan M Stokes, Joseph H Davis, Chand S Mangat, James R Williamson, Eric D Brown

Open access · goldAbstract read
In one paragraph

Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

54 citing papers in PubMed, 91 citations in OpenAlex.

  1. Review
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  9. Lamotrigine-mediated rescue of RsgA-deficientJournal of bacteriology · 2024
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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

5 authors at 2 institutions in 2 countries.

Jonathan M StokesMichael G DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
Joseph H DavisDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States.
Chand S MangatMichael G DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
James R WilliamsonDepartment of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States.
Eric D BrownMichael G DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.
McMaster University · CAScripps Research Institute · US

Funding

Assembly of E. coli ribosomes in vitro and in cellsR37GM053757 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI WILLIAMSON, JAMES R · 2008 to 2017
$5.1M
CIHRNIGMS NIH HHS R37 GM053757NIGMS NIH HHS R37-GM053757
6 · The paper itself

Abstract

While small molecule inhibitors of the bacterial ribosome have been instrumental in understanding protein translation, no such probes exist to study ribosome biogenesis. We screened a diverse chemical collection that included previously approved drugs for compounds that induced cold sensitive growth inhibition in the model bacterium Escherichia coli. Among the most cold sensitive was lamotrigine, an anticonvulsant drug. Lamotrigine treatment resulted in the rapid accumulation of immature 30S and 50S ribosomal subunits at 15 °C. Importantly, this was not the result of translation inhibition, as lamotrigine was incapable of perturbing protein synthesis in vivo or in vitro. Spontaneous suppressor mutations blocking lamotrigine activity mapped solely to the poorly characterized domain II of translation initiation factor IF2 and prevented the binding of lamotrigine to IF2 in vitro. This work establishes lamotrigine as a widely available chemical probe of bacterial ribosome biogenesis and suggests a role for E. coli IF2 in ribosome assembly.

Indexed as

Amino Acid SequenceCold TemperatureEscherichia coliLamotrigineMolecular Sequence DataProkaryotic Initiation Factor-2Protein BiosynthesisRibosomesRibosome Subunits, Large, BacterialRibosome Subunits, Small, BacterialSmall Molecule LibrariesStress, PhysiologicalTriazinesLamotrigineProkaryotic Initiation Factor-2Small Molecule LibrariesTriazinesbiochemistrycold sensitivityE. coliinfectious diseaselamotriginemicrobiologyribosome biogenesistranslation initiation factor IF2

Identifiers

PMID25233066
PMCPMC4371806
OpenAlexW1998063413

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.