Evidence map›Paper›PMID 23750903›Full record

ArticleMolecular microbiology2013

Genetic and structural validation of Aspergillus fumigatus UDP-N-acetylglucosamine pyrophosphorylase as an antifungal target.

Wenxia Fang, Ting Du, Olawale G Raimi, Ramon Hurtado-Guerrero, Michael D Urbaniak, Adel F M Ibrahim, Michael A J Ferguson, Cheng Jin, Daan M F van Aalten

Open access · hybridAbstract read
In one paragraph

Article in Molecular microbiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
0.3field-weighted citation impact, top 37% 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

23 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  3. Compromising UDP-sugar nucleotide biosynthesis attenuatesCell surface (Amsterdam, Netherlands) · 2026
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  7. Article
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  9. Chitin Biosynthesis inJournal of fungi (Basel, Switzerland) · 2023
    Review
  10. Article
  11. Article
  12. Article
  13. The citron homology domain as a scaffold for Rho1 signaling.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  14. Article
  15. Article
  16. UDP-Frontiers in plant science · 2021
    Article
  17. Targeting a critical step in fungal hexosamine biosynthesis.The Journal of biological chemistry · 2020
    Article
  18. A mechanism-inspired UDP-RSC chemical biology · 2020
    Article
  19. Article
  20. Article
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

9 authors at 3 institutions in 2 countries.

Wenxia FangDivision of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK.
Ting Du
Olawale G Raimi
Ramon Hurtado-Guerrero
Michael D Urbaniak
Adel F M Ibrahim
Michael A J Ferguson
Cheng Jin
Daan M F van Aalten
University of Dundee · GBChinese Academy of Sciences · CNInstitute of Microbiology · CN

Funding

Medical Research Council G0900138Wellcome Trust 087590Wellcome Trust WT087590MA
6 · The paper itself

Abstract

The sugar nucleotide UDP-N-acetylglucosamine (UDP-GlcNAc) is an essential metabolite in both prokaryotes and eukaryotes. In fungi, it is the precursor for the synthesis of chitin, an essential component of the fungal cell wall. UDP-N-acetylglucosamine pyrophosphorylase (UAP) is the final enzyme in eukaryotic UDP-GlcNAc biosynthesis, converting UTP and N-acetylglucosamine-1-phosphate (GlcNAc-1P) to UDP-GlcNAc. As such, this enzyme may provide an attractive target against pathogenic fungi. Here, we demonstrate that the fungal pathogen Aspergillus fumigatus possesses an active UAP (AfUAP1) that shows selectivity for GlcNAc-1P as the phosphosugar substrate. A conditional mutant, constructed by replacing the native promoter of the A. fumigatus uap1 gene with the Aspergillus nidulans alcA promoter, revealed that uap1 is essential for cell survival and important for cell wall synthesis and morphogenesis. The crystal structure of AfUAP1 was determined and revealed exploitable differences in the active site compared with the human enzyme. Thus AfUAP1 could represent a novel antifungal target and this work will assist the future discovery of small molecule inhibitors against this enzyme.

Indexed as

AcetylglucosamineAspergillus fumigatusCell WallCloning, MolecularFungal ProteinsGenes, EssentialMutationNucleotidyltransferasesPromoter Regions, GeneticProtein Structure, TertiarySubstrate SpecificityAcetylglucosamineFungal ProteinsN-acetylglucosamine-1-phosphateNucleotidyltransferasesUDPacetylglucosamine pyrophosphorylase

Identifiers

PMID23750903
PMCPMC3888555
OpenAlexW2146672483

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.