Evidence map›Paper›PMID 36682579›Full record

ArticleAnalytical biochemistry2023

Screening for small molecule inhibitors of SAH nucleosidase using an SAH riboswitch.

Harini Sadeeshkumar, Aparaajita Balaji, Alan G Sutherland, Saraspadee Mootien, Karen G Anthony, Ronald R Breaker

Open access · greenAbstract read
In one paragraph

Article in Analytical biochemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. The Spermidine Synthase Gene as a Reporter of Transcription Inhibition inInternational journal of molecular sciences · 2026
    Article
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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

6 authors at 2 institutions in 1 country.

Harini SadeeshkumarDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, 06520-8103, USA.
Aparaajita BalajiDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, 06520-8103, USA.
Alan G SutherlandL2 Diagnostics, LLC, 300 George Street, New Haven, CT, 06511, USA.
Saraspadee MootienL2 Diagnostics, LLC, 300 George Street, New Haven, CT, 06511, USA.
Karen G AnthonyL2 Diagnostics, LLC, 300 George Street, New Haven, CT, 06511, USA.
Ronald R BreakerDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, 06520-8103, USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, 06520-8103, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT, 06520-8103, USA. Electronic address: ronald.breaker@yale.edu.
Yale University · USHoward Hughes Medical Institute · US

Funding

Skill Development for Diverse Scientific Careers: A New Course Predoctoral Program in Cellular and Molecular BiologyT32GM007223 · NIGMS · YALE UNIVERSITY · PI BASERGA, SUSAN J · 1985 to 2019
$31.0M
X-RAY ANALYSIS OF PROTEIN STRUCTURE AND FUNCTIONP01GM022778 · NIGMS · YALE UNIVERSITY · PI BREAKER, RONALD R · 1985 to 2019
$26.1M
Predoc Training at the Interface Chemistry and BiologyT32GM067543 · NIGMS · YALE UNIVERSITY · PI CRAWFORD, JASON MICHAEL · 2003 to 2022
$7.4M
Exploiting Riboswitch Sensors to Reveal Antibiotics Uptake and Retention in Gram Negative BacteriaR01AI136794 · NIAID · YALE UNIVERSITY · PI BREAKER, RONALD R, KAZMIERCZAK, BARBARA I · 2018 to 2022
$5.6M
Howard Hughes Medical InstituteNIAID NIH HHS R01 AI136794NIGMS NIH HHS P01 GM022778NIGMS NIH HHS T32 GM007223NIGMS NIH HHS T32 GM067543
6 · The paper itself

Abstract

Due to the emergence of multidrug resistant pathogens, it is imperative to identify new targets for antibiotic drug discovery. The S-adenosylhomocysteine (SAH) nucleosidase enzyme is a promising target for antimicrobial drug development due to its critical functions in multiple bacterial processes including recycling of toxic byproducts of S-adenosylmethionine (SAM)-mediated reactions and producing the precursor of the universal quorum sensing signal, autoinducer-2 (AI-2). Riboswitches are structured RNA elements typically used by bacteria to precisely monitor and respond to changes in essential bacterial processes, including metabolism. Natural riboswitches fused to a reporter gene can be exploited to detect changes in metabolism or in physiological signaling. We performed a high-throughput screen (HTS) using an SAH-riboswitch controlled β-galactosidase reporter gene in Escherichia coli to discover small molecules that inhibit SAH recycling. We demonstrate that the assay strategy using SAH riboswitches to detect the effects of SAH nucleosidase inhibitors can quickly identify compounds that penetrate the barriers of Gram-negative bacterial cells and perturb pathways involving SAH.

Indexed as

RiboswitchBacteriaN-Glycosyl HydrolasesRNAS-AdenosylmethionineN-Glycosyl HydrolasesRiboswitchRNAS-AdenosylmethionineAntibioticsHigh-throughput screeningNoncoding RNAS-adenosylhomocysteineS-adenosylmethionine

Identifiers

PMID36682579
PMCPMC11149561
OpenAlexW4317528922

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.