Evidence map›Paper›PMID 27624005›Full record

ArticleScientific reports2016

The Crystal Structure of Peroxiredoxin Asp f3 Provides Mechanistic Insight into Oxidative Stress Resistance and Virulence of Aspergillus fumigatus.

Falk Hillmann, Karine Bagramyan, Maria Straßburger, Thorsten Heinekamp, Teresa B Hong, Krzysztof P Bzymek, John C Williams, Axel A Brakhage, Markus Kalkum

Abstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
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

26 citing papers in PubMed.

  1. Article
  2. Article
  3. Residential exposure toThe European respiratory journal · 2024
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Oxidative stress response pathways in fungi.Cellular and molecular life sciences : CMLS · 2022
    Review
  10. Sulfur Metabolism as a Promising Source of New Antifungal Targets.Journal of fungi (Basel, Switzerland) · 2022
    Review
  11. Article
  12. Increasing NADPH impairs fungal HBioresources and bioprocessing · 2022
    Article
  13. Article
  14. Relevance of peroxiredoxins in pathogenic microorganisms.Applied microbiology and biotechnology · 2021
    Review
  15. Article
  16. Article
  17. Review
  18. 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.

Falk HillmannJunior Research Group Evolution of Microbial Interactions, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institut, Beutenbergstrasse 11a, D-07745 Jena, Germany.
Karine BagramyanDepartment of Molecular Immunology, The Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
Maria StraßburgerTransfer Group Anti-infectives, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institut, Beutenbergstrasse 11a, D-07745 Jena, Germany.
Thorsten HeinekampDepartment of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institut, Beutenbergstrasse 11a, D-07745 Jena, Germany.
Teresa B HongDepartment of Molecular Immunology, The Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
Krzysztof P BzymekDepartment of Molecular Medicine, The Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
John C WilliamsDepartment of Molecular Medicine, The Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.
Axel A BrakhageDepartment of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institut, Beutenbergstrasse 11a, D-07745 Jena, Germany.
Markus KalkumDepartment of Molecular Immunology, The Beckman Research Institute of City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA.

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
NCI NIH HHS P30 CA033572
6 · The paper itself

Abstract

Invasive aspergillosis and other fungal infections occur in immunocompromised individuals, including patients who received blood-building stem cell transplants, patients with chronic granulomatous disease (CGD), and others. Production of reactive oxygen species (ROS) by immune cells, which incidentally is defective in CGD patients, is considered to be a fundamental process in inflammation and antifungal immune response. Here we show that the peroxiredoxin Asp f3 of Aspergillus fumigatus inactivates ROS. We report the crystal structure and the catalytic mechanism of Asp f3, a two-cysteine type peroxiredoxin. The latter exhibits a thioredoxin fold and a homodimeric structure with two intermolecular disulfide bonds in its oxidized state. Replacement of the Asp f3 cysteines with serine residues retained its dimeric structure, but diminished Asp f3's peroxidase activity, and extended the alpha-helix with the former peroxidatic cysteine residue C61 by six residues. The asp f3 deletion mutant was sensitive to ROS, and this phenotype was rescued by ectopic expression of Asp f3. Furthermore, we showed that deletion of asp f3 rendered A. fumigatus avirulent in a mouse model of pulmonary aspergillosis. The conserved expression of Asp f3 homologs in medically relevant molds and yeasts prompts future evaluation of Asp f3 as a potential therapeutic target.

Indexed as

Oxidative StressAnimalsAspergillosisAspergillus fumigatusCrystallography, X-RayFemaleFungal ProteinsGene DeletionKineticsMiceModels, MolecularMutant ProteinsOxidation-ReductionPeroxidasePeroxiredoxinsProtein MultimerizationFungal ProteinsMutant ProteinsPeroxidasePeroxiredoxinsSuperoxides

Identifiers

PMID27624005
PMCPMC5022050

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Registered trials

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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.