Evidence map›Paper›PMID 26864964›Full record

ArticleFEBS letters2016

Novel motif in calcineurin catalytic subunit is required for septal localization of calcineurin in Aspergillus fumigatus.

Praveen R Juvvadi, Charles W Pemble, Yan Ma, William J Steinbach

Open access · bronzeAbstract read
In one paragraph

Article in FEBS letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Potential Antifungal Targets forInternational journal of molecular sciences · 2022
    Review
  3. Aspergillus fumigatus and Aspergillosis in 2019.Clinical microbiology reviews · 2019
    Review
  4. Article
  5. Article
  6. Review
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

4 authors at 3 institutions in 2 countries.

Praveen R JuvvadiDivision of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Charles W PembleDuke Macromolecular Crystallography Center, Duke University Medical Center, Durham, NC, USA.
Yan MaDepartment of Dermatology and Venereology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
William J SteinbachDivision of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Duke Medical Center · USDuke University Hospital · USShanxi Medical University · CN

Funding

Trehalose Pathway for Antifungal Targets and InhibitorsP01AI104533 · NIAID · DUKE UNIVERSITY · PI PERFECT, JOHN R. · 2015 to 2019
$9.0M
Structural Biological Development of Fungal-Specific Calcineurin InhibitorsR01AI112595 · NIAID · DUKE UNIVERSITY · PI HEITMAN, JOSEPH, SCHUMACHER, MARIA · 2014 to 2017
$2.5M
NIAID NIH HHS P01 AI104533NIAID NIH HHS R01 AI112595NIAID NIH HHS R01 AI112595-01
6 · The paper itself

Abstract

Calcineurin heterodimer, comprised of the catalytic (CnaA) and regulatory (CnaB) subunits, localizes at the hyphal tips and septa to direct growth, septation, and disease in the human pathogen Aspergillus fumigatus. Here we discovered a novel motif (FMDVF) required for this critical CnaA septal localization, including residues Phe368, Asp370 and Phe372 overlapping the cyclosporine A-cyclophilin A-binding domain, CnaB-binding helix and the FK506-FKBP12-binding pocket. Mutations in adjacent residues Asn367, Trp374, and Ser375 confer FK506 resistance without impacting CnaA septal localization. Modeling A. fumigatus CnaA confirmed that the FMDVF motif forms a bridge between the two known substrate-binding motifs, PxIxIT and LxVP, and concurrent mutations (F368A D370A; F368A F372A) in the FMDVF motif disrupt CnaA-substrate interaction at the septum.

Indexed as

Catalytic DomainAmino Acid MotifsAspergillus fumigatusCalcineurinCyclophilin ACyclosporineDrug Resistance, FungalFungal ProteinsHyphaeMolecular Sequence DataMutationProtein MultimerizationSubstrate SpecificityTacrolimusCalcineurinCyclophilin ACyclosporineFungal ProteinsTacrolimusAspergillus fumigatuscalcineurinFK506LxVP motifPxIxIT motifseptum

Identifiers

PMID26864964
PMCPMC4764407
OpenAlexW2260356498

What OpenQuestion holds

Textmetadata
LicenceTDM
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.