Evidence map›Paper›PMID 31785178›Full record

ArticleThe FEBS journal2020

On the mechanism of calcium-dependent activation of NADPH oxidase 5 (NOX5).

Elisa Millana Fañanás, Sofia Todesca, Alessandro Sicorello, Laura Masino, Petr Pompach, Francesca Magnani, Annalisa Pastore, Andrea Mattevi

Abstract read
In one paragraph

Article in The FEBS journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Enhancing Selectivity and Potency of SJournal of medicinal chemistry · 2025
    Article
  6. Structural basis of human NOX5 activation.Nature communications · 2024
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Physiologically Relevant Free CaJournal of molecular biology · 2021
    Article
  18. Article
  19. Oxidative Stress and Hypertension.Circulation research · 2021
    Review
  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

8 authors.

Elisa Millana FañanásDepartment of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Italy.
Sofia TodescaDepartment of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Italy.
Alessandro SicorelloUK Dementia Research Institute at King's College London, UK.
Laura MasinoThe Crick Institute, London, UK.
Petr PompachInstitute of Biotechnology, Czech Academy of Sciences, Vestec, Czech Republic.
Francesca MagnaniDepartment of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Italy.
Annalisa PastoreUK Dementia Research Institute at King's College London, UK.ORCID 0000-0002-3047-654X
Andrea MatteviDepartment of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, Italy.ORCID 0000-0002-9523-7128

Funding

Cancer Research UKMedical Research Council FC001029Medical Research Council MC_U117533887Medical Research Council MC_U117584256Wellcome Trust 731077Wellcome Trust FC001029
6 · The paper itself

Abstract

It is now accepted that reactive oxygen species (ROS) are not only dangerous oxidative agents but also chemical mediators of the redox cell signaling and innate immune response. A central role in ROS-controlled production is played by the NADPH oxidases (NOXs), a group of seven membrane-bound enzymes (NOX1-5 and DUOX1-2) whose unique function is to produce ROS. Here, we describe the regulation of NOX5, a widespread family member present in cyanobacteria, protists, plants, fungi, and the animal kingdom. We show that the calmodulin-like regulatory EF-domain of NOX5 is partially unfolded and detached from the rest of the protein in the absence of calcium. In the presence of calcium, the C-terminal lobe of the EF-domain acquires an ordered and more compact structure that enables its binding to the enzyme dehydrogenase (DH) domain. Our spectroscopic and mutagenesis studies further identified a set of conserved aspartate residues in the DH domain that are essential for NOX5 activation. Altogether, our work shows that calcium induces an unfolded-to-folded transition of the EF-domain that promotes direct interaction with a conserved regulatory region, resulting in NOX5 activation.

Indexed as

CalciumCrystallography, X-RayCyanobacteriaHumansModels, MolecularNADPH Oxidase 5Protein ConformationReactive Oxygen SpeciesCalciumNADPH Oxidase 5Reactive Oxygen Speciescalcium activationEF-handsenzymeNMRstructure

Identifiers

PMID31785178
PMCPMC7317449

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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.