Evidence map›Paper›PMID 24699450›Full record

ArticlePloS one2014

Studies on inhibition of respiratory cytochrome bc1 complex by the fungicide pyrimorph suggest a novel inhibitory mechanism.

Yu-Mei Xiao, Lothar Esser, Fei Zhou, Chang Li, Yi-Hui Zhou, Chang-An Yu, Zhao-Hai Qin, Di Xia

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
4.1field-weighted citation impact, top 7% 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

12 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Crystal structure of bacterial cytochromeThe Journal of biological chemistry · 2019
    Article
  9. Review
  10. Article
  11. Toxicity of fungicides toRSC advances · 2018
    Article
  12. 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 at 4 institutions in 2 countries.

Yu-Mei XiaoDepartment of Applied Chemistry, China Agricultural University, Beijing, China; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Lothar EsserLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Fei ZhouLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Chang LiDepartment of Applied Chemistry, China Agricultural University, Beijing, China.
Yi-Hui ZhouDepartment of Applied Chemistry, China Agricultural University, Beijing, China; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
Chang-An YuDepartment of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma, United States of America.
Zhao-Hai QinDepartment of Applied Chemistry, China Agricultural University, Beijing, China.
Di XiaLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, United States of America.
China Agricultural University · CNCenter for Cancer Research · USNational Cancer Institute · USOklahoma State University · US

Funding

Structural Basis of Biological Membrane Protein Functions and Drug ResistanceZIABC010319 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI XIA, DI S · 2009 to 2025
$22.7M
Intramural NIH HHS
6 · The paper itself

Abstract

The respiratory chain cytochrome bc1 complex (cyt bc1) is a major target of numerous antibiotics and fungicides. All cyt bc1 inhibitors act on either the ubiquinol oxidation (QP) or ubiquinone reduction (QN) site. The primary cause of resistance to bc1 inhibitors is target site mutations, creating a need for novel agents that act on alternative sites within the cyt bc1 to overcome resistance. Pyrimorph, a synthetic fungicide, inhibits the growth of a broad range of plant pathogenic fungi, though little is known concerning its mechanism of action. In this study, using isolated mitochondria from pathogenic fungus Phytophthora capsici, we show that pyrimorph blocks mitochondrial electron transport by affecting the function of cyt bc1. Indeed, pyrimorph inhibits the activities of both purified 11-subunit mitochondrial and 4-subunit bacterial bc1 with IC50 values of 85.0 μM and 69.2 μM, respectively, indicating that it targets the essential subunits of cyt bc1 complexes. Using an array of biochemical and spectral methods, we show that pyrimorph acts on an area near the QP site and falls into the category of a mixed-type, noncompetitive inhibitor with respect to the substrate ubiquinol. In silico molecular docking of pyrimorph to cyt b from mammalian and bacterial sources also suggests that pyrimorph binds in the vicinity of the quinol oxidation site.

Indexed as

AcrylamidesAnimalsCattleElectron TransportElectron Transport Complex IIIFungicides, IndustrialMitochondriaMorpholinesAcrylamidesElectron Transport Complex IIIFungicides, IndustrialMorpholinespyrimorph

Identifiers

PMID24699450
PMCPMC3974799
OpenAlexW1997885377

What OpenQuestion holds

Textmetadata
LicenceCC0
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.