Evidence map›Paper›PMID 23844980›Full record

ArticleBioscience reports2013

Genetic and structural validation of Aspergillus fumigatus N-acetylphosphoglucosamine mutase as an antifungal target.

Wenxia Fang, Ting Du, Olawale G Raimi, Ramón Hurtado-Guerrero, Karina Mariño, Adel F M Ibrahim, Osama Albarbarawi, Michael A J Ferguson, Cheng Jin, Daan M F Van Aalten

Open access · goldAbstract read
In one paragraph

Article in Bioscience reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

17 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. Compromising UDP-sugar nucleotide biosynthesis attenuatesCell surface (Amsterdam, Netherlands) · 2026
    Article
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  4. Article
  5. Article
  6. Article
  7. Cells · 2023
    Review
  8. Article
  9. Article
  10. SsAGM1-Mediated Uridine Diphosphate-Frontiers in microbiology · 2022
    Article
  11. Targeting a critical step in fungal hexosamine biosynthesis.The Journal of biological chemistry · 2020
    Article
  12. Article
  13. Evidence for substrate-assisted catalysis inThe Biochemical journal · 2018
    Article
  14. Article
  15. Article
  16. Article
  17. 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

10 authors at 2 institutions in 1 country.

Wenxia Fang*Division of Molecular Microbiology, University of Dundee, DD1 5EH, Scotland, U.K.
Ting Du†State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
Olawale G Raimi*Division of Molecular Microbiology, University of Dundee, DD1 5EH, Scotland, U.K.
Ramón Hurtado-Guerrero*Division of Molecular Microbiology, University of Dundee, DD1 5EH, Scotland, U.K.
Karina Mariño‡Division of Biological Chemistry and Drug Discovery, University of Dundee, DD1 5EH, Scotland, U.K.
Adel F M Ibrahim§The College of Life Sciences Cloning Team, College of Life Sciences, University of Dundee, DD1 5EH, Scotland, U.K.
Osama Albarbarawi*Division of Molecular Microbiology, University of Dundee, DD1 5EH, Scotland, U.K.
Michael A J Ferguson‡Division of Biological Chemistry and Drug Discovery, University of Dundee, DD1 5EH, Scotland, U.K.
Cheng Jin†State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China.
Daan M F Van Aalten*Division of Molecular Microbiology, University of Dundee, DD1 5EH, Scotland, U.K.
Chinese Academy of Sciences · CNInstitute of Microbiology · CN

Funding

Medical Research Council G0900138Wellcome Trust 085622Wellcome Trust 087590Wellcome Trust WT087590MA
6 · The paper itself

Abstract

Aspergillus fumigatus is the causative agent of IA (invasive aspergillosis) in immunocompromised patients. It possesses a cell wall composed of chitin, glucan and galactomannan, polymeric carbohydrates synthesized by processive glycosyltransferases from intracellular sugar nucleotide donors. Here we demonstrate that A. fumigatus possesses an active AfAGM1 (A. fumigatus N-acetylphosphoglucosamine mutase), a key enzyme in the biosynthesis of UDP (uridine diphosphate)-GlcNAc (N-acetylglucosamine), the nucleotide sugar donor for chitin synthesis. A conditional agm1 mutant revealed the gene to be essential. Reduced expression of agm1 resulted in retarded cell growth and altered cell wall ultrastructure and composition. The crystal structure of AfAGM1 revealed an amino acid change in the active site compared with the human enzyme, which could be exploitable in the design of selective inhibitors. AfAGM1 inhibitors were discovered by high-throughput screening, inhibiting the enzyme with IC50s in the low μM range. Together, these data provide a platform for the future development of AfAGM1 inhibitors with antifungal activity.

Indexed as

Antifungal AgentsAspergillus fumigatusCatalytic DomainCell WallCrystallography, X-RayFungal ProteinsHumansInhibitory Concentration 50KineticsMagnesiumMicrobial Sensitivity TestsMicrobial ViabilityModels, MolecularPhosphotransferases (Phosphomutases)Protein Structure, SecondaryAntifungal AgentsFungal ProteinsMagnesiumPhosphotransferases (Phosphomutases)

Identifiers

PMID23844980
PMCPMC3763426
OpenAlexW2157729291

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.