Evidence map›Paper›PMID 30388443›Full record

ArticleCell2018

Structures of DPAGT1 Explain Glycosylation Disease Mechanisms and Advance TB Antibiotic Design.

Yin Yao Dong, Hua Wang, Ashley C W Pike, Stephen A Cochrane, Sadra Hamedzadeh, Filip J Wyszyński, Simon R Bushell, Sylvain F Royer, David A Widdick, Andaleeb Sajid and 22 more

Open access · hybridAbstract read
In one paragraph

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

52 citing papers in PubMed, 86 citations in OpenAlex.

  1. Article
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  8. Lipid II unlocked: strategies for obtaining a major antibiotic target.Chemical communications (Cambridge, England) · 2025
    Review
  9. DPAGT1-Perspective as an Anticancer Drug Target.Molecules (Basel, Switzerland) · 2025
    Review
  10. "Design principles of a membrane-spanning ubiquitin ligase".bioRxiv : the preprint server for biology · 2025
    Article
  11. Article
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  14. Article
  15. Review
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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

32 authors at 6 institutions in 2 countries.

Yin Yao DongStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Hua WangChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Ashley C W PikeStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Stephen A CochraneChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK; School of Chemistry and Chemical Engineering, Queen's University, Belfast, UK.
Sadra HamedzadehChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Filip J WyszyńskiChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Simon R BushellStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Sylvain F RoyerChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
David A WiddickDepartment of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, UK.
Andaleeb SajidTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Helena I BoshoffTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Yumi ParkTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Ricardo LucasChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Wei-Min LiuChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Seung Seo LeeChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Takuya MachidaChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Leanne MinallChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK.
Shahid MehmoodDepartment of Chemistry, Oxford, OX1 3QZ, UK.
Katsiaryna BelayaNeurosciences Group, Nuffield Department of Clinical Neuroscience, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Wei-Wei LiuNeurosciences Group, Nuffield Department of Clinical Neuroscience, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Amy ChuStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Leela ShresthaStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Shubhashish M M MukhopadhyayStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Claire Strain-DamerellStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Rod ChalkStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Nicola A Burgess-BrownStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK.
Mervyn J BibbDepartment of Molecular Microbiology, John Innes Centre, Norwich, NR4 7UH, UK.
Clifton E Barry IiiTuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Carol V RobinsonDepartment of Chemistry, Oxford, OX1 3QZ, UK.
David BeesonNeurosciences Group, Nuffield Department of Clinical Neuroscience, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Benjamin G DavisChemistry Research Laboratory, University of Oxford, Oxford, OX1 3TA, UK. Electronic address: Ben.Davis@chem.ox.ac.uk.
Elisabeth P CarpenterStructural Genomics Consortium, University of Oxford, Oxford, OX3 7DQ, UK. Electronic address: liz.carpenter@sgc.ox.ac.uk.
University of Oxford · GBGenomics (United Kingdom) · GBNational Institute of Allergy and Infectious Diseases · USJohn Innes Centre · GBMRC Weatherall Institute of Molecular Medicine · GBNational Institutes of Health · US

Funding

Development Of New Chemotherapeutics For TuberculosisZIAAI000693 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BARRY, CLIFTON · 2009 to 2025
$20.1M
Biotechnology and Biological Sciences Research Council BB/J004561/1Biotechnology and Biological Sciences Research Council BB/J006637/1Biotechnology and Biological Sciences Research Council BB/J009725/1Intramural NIH HHS ZIA AI000693Medical Research Council MR/M006824/1Medical Research Council MR/N020413/1Wellcome TrustWellcome Trust 106169/Z/14/ZWellcome Trust 110270/A/15/ZWellcome Trust WT084655MA
6 · The paper itself

Abstract

Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic "lipid-altered" tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug.

Indexed as

AnimalsAntibiotics, AntitubercularBinding SitesCongenital Disorders of GlycosylationEnzyme InhibitorsFemaleHEK293 CellsHep G2 CellsHumansLipid MetabolismMiceMolecular Docking SimulationMutationN-AcetylglucosaminyltransferasesProtein BindingSf9 CellsAntibiotics, Antituberculardolichyl-phosphate alpha-N-acetylglucosaminyltransferaseEnzyme InhibitorsN-AcetylglucosaminyltransferasesTunicamycinUridine Diphosphate Glucuronic Acidcongenital disorders of glycosylationcongenital myasthenic syndromeDPAGT1GPTProtein N-glycosylationtunicamycin

Identifiers

PMID30388443
PMCPMC6218659
OpenAlexW2795719567

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.