Evidence map›Paper›PMID 36266336›Full record

ArticleNature microbiology2022

CRISPR-based oligo recombineering prioritizes apicomplexan cysteines for drug discovery.

H J Benns, M Storch, J A Falco, F R Fisher, F Tamaki, E Alves, C J Wincott, R Milne, N Wiedemar, G Craven and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Proteomics Applications inPathogens (Basel, Switzerland) · 2023
    Review
  6. Article
  7. Article
  8. Multi-omic stratification of the missense variant cysteinome.bioRxiv : the preprint server for biology · 2023
    Article
  9. Article
  10. iScience · 2023
    Article
  11. Article
  12. Article
  13. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 3 countries.

H J BennsDepartment of Life Sciences, Imperial College London, London, UK.
M StorchLondon Biofoundry, Imperial College Translation & Innovation Hub, London, UK.
J A FalcoDepartment of Chemistry, Boston College, Boston, MA, USA.
F R FisherDepartment of Life Sciences, Imperial College London, London, UK.
F TamakiWellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, UK.
E AlvesDepartment of Life Sciences, Imperial College London, London, UK.
C J WincottDepartment of Life Sciences, Imperial College London, London, UK.
R MilneWellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, UK.
N WiedemarWellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, UK.
G CravenDepartment of Chemistry, Imperial College London, London, UK.
B BaragañaWellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, UK.
S WyllieWellcome Centre for Anti-Infectives Research, School of Life Sciences, University of Dundee, Dundee, UK.
J BaumDepartment of Life Sciences, Imperial College London, London, UK.
G S BaldwinDepartment of Life Sciences, Imperial College London, London, UK.
E WeerapanaDepartment of Chemistry, Boston College, Boston, MA, USA.
E W TateDepartment of Chemistry, Imperial College London, London, UK. e.tate@imperial.ac.uk.
M A ChildDepartment of Life Sciences, Imperial College London, London, UK. m.child@imperial.ac.uk.ORCID 0000-0002-1565-5638
Imperial College London · GBUniversity of Dundee · GBBoston College · USLondon Biofoundry · GBUNSW Sydney · AU

Funding

Developing chemical-proteomic tools to investigate cysteine oxidationR35GM134964 · NIGMS · BOSTON COLLEGE · PI WEERAPANA, ERANTHIE · 2020 to 2024
$3.1M
Biotechnology and Biological Sciences Research Council BB/M011178/1NIGMS NIH HHS R35 GM134964Wellcome Trust 100993/Z/13/ZWellcome Trust 202553/Z/16/ZWellcome Trust 203134/Z/16/Z
6 · The paper itself

Abstract

Nucleophilic amino acids are important in covalent drug development yet underutilized as anti-microbial targets. Chemoproteomic technologies have been developed to mine chemically accessible residues via their intrinsic reactivity towards electrophilic probes but cannot discern which chemically reactive sites contribute to protein function and should therefore be prioritized for drug discovery. To address this, we have developed a CRISPR-based oligo recombineering (CORe) platform to support the rapid identification, functional prioritization and rational targeting of chemically reactive sites in haploid systems. Our approach couples protein sequence and function with biological fitness of live cells. Here we profile the electrophile sensitivity of proteinogenic cysteines in the eukaryotic pathogen Toxoplasma gondii and prioritize functional sites using CORe. Electrophile-sensitive cysteines decorating the ribosome were found to be critical for parasite growth, with target-based screening identifying a parasite-selective anti-malarial lead molecule and validating the apicomplexan translation machinery as a target for ongoing covalent ligand development.

Indexed as

ToxoplasmaAmino Acid SequenceCysteineDrug DiscoveryProtein Processing, Post-TranslationalCysteine

Identifiers

PMID36266336
PMCPMC9613468
OpenAlexW4306888740

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.