Evidence map›Paper›PMID 25728269›Full record

ArticleChemistry & biology2015

Global analysis of protein N-myristoylation and exploration of N-myristoyltransferase as a drug target in the neglected human pathogen Leishmania donovani.

Megan H Wright, Daniel Paape, Elisabeth M Storck, Remigiusz A Serwa, Deborah F Smith, Edward W Tate

Open access · hybridAbstract read
In one paragraph

Article in Chemistry & biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
9.9field-weighted citation impact, top 2% 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

45 citing papers in PubMed, 83 citations in OpenAlex.

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  13. Screening of medicinal plants unraveled the leishmanicidal credibility ofJournal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022
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  19. Novel Thienopyrimidine Inhibitors ofJournal of medicinal chemistry · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Megan H WrightDepartment of Chemistry, Imperial College London, London SW7 2AZ, UK. Electronic address: megan.wright@tum.de.
Daniel PaapeCentre for Immunology and Infection, Department of Biology, University of York, York YO10 5DD, UK.
Elisabeth M StorckDepartment of Chemistry, Imperial College London, London SW7 2AZ, UK.
Remigiusz A SerwaDepartment of Chemistry, Imperial College London, London SW7 2AZ, UK.
Deborah F SmithCentre for Immunology and Infection, Department of Biology, University of York, York YO10 5DD, UK.
Edward W TateDepartment of Chemistry, Imperial College London, London SW7 2AZ, UK. Electronic address: e.tate@imperial.ac.uk.
Imperial College London · GBUniversity of York · GB

Funding

Biotechnology and Biological Sciences Research Council BB/D02014X/1British Heart FoundationMedical Research Council MR/L000148/1Wellcome Trust 087792
6 · The paper itself

Abstract

N-Myristoyltransferase (NMT) modulates protein function through the attachment of the lipid myristate to the N terminus of target proteins, and is a promising drug target in eukaryotic parasites such as Leishmania donovani. Only a small number of NMT substrates have been characterized in Leishmania, and a global picture of N-myristoylation is lacking. Here, we use metabolic tagging with an alkyne-functionalized myristic acid mimetic in live parasites followed by downstream click chemistry and analysis to identify lipidated proteins in both the promastigote (extracellular) and amastigote (intracellular) life stages. Quantitative chemical proteomics is used to profile target engagement by NMT inhibitors, and to define the complement of N-myristoylated proteins. Our results provide new insight into the multiple pathways modulated by NMT and the pleiotropic effects of NMT inhibition. This work constitutes the first global experimental analysis of protein lipidation in Leishmania, and reveals the extent of NMT-related biology yet to be explored for this neglected human pathogen.

Indexed as

AcyltransferasesAnimalsHumansLeishmania donovaniLeishmaniasisMiceMice, Inbred BALB CMice, KnockoutMyristatesProtein Processing, Post-TranslationalProteomicsProtozoan ProteinsAcyltransferasesglycylpeptide N-tetradecanoyltransferaseMyristatesProtozoan Proteins

Identifiers

PMID25728269
PMCPMC4372256
OpenAlexW1980135244

What OpenQuestion holds

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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.