Evidence map›Paper›PMID 14742718›Full record

ArticleMolecular biology of the cell2004

Dinitroanilines bind alpha-tubulin to disrupt microtubules.

Naomi S Morrissette, Arpita Mitra, David Sept, L David Sibley

Open access · greenAbstract read
In one paragraph

Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

67 citing papers in PubMed, 155 citations in OpenAlex.

  1. Article
  2. mBio · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Cryo-ET ofProceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

7 more citing papers are in PubMed but not listed here.

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 1 institution in 1 country.

Naomi S MorrissetteDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. naomi@borcim.wustl.edu
Arpita Mitra
David Sept
L David Sibley
Washington University in St. Louis · US

Funding

PROTEIN SECRETION &INTRACELLULAR SURVIVAL BY TOXOPLASMAR01AI034036 · NIAID · WASHINGTON UNIVERSITY · PI SIBLEY, L. DAVID · 1993 to 2019
$7.9M
Mechanisms of Dinitroaniline Action, Selectivity and ResistanceR01AI067981 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI MORRISSETTE, NAOMI S · 2006 to 2010
$1.7M
Toxoplasma and Plasmodium resistance to dinitroanilinesF32GM020484 · NIGMS · WASHINGTON UNIVERSITY · PI MORRISSETTE, NAOMI S · 2001 to 2002
$75k
NIAID NIH HHS R01 AI034036NIAID NIH HHS R01 AI067981NIAID NIH HHS T32 AI07017221NIGMS NIH HHS F32 GM020484NIGMS NIH HHS F32 GM20484-01A1
6 · The paper itself

Abstract

Protozoan parasites are remarkably sensitive to dinitroanilines such as oryzalin, which disrupt plant but not animal microtubules. To explore the basis of dinitroaniline action, we isolated 49 independent resistant Toxoplasma gondii lines after chemical mutagenesis. All 23 of the lines that we examined harbored single point mutations in alpha-tubulin. These point mutations were sufficient to confer resistance when transfected into wild-type parasites. Several mutations were in the M or N loops, which coordinate protofilament interactions in the microtubule, but most of the mutations were in the core of alpha-tubulin. Docking studies predict that oryzalin binds with an average affinity of 23 nM to a site located beneath the N loop of Toxoplasma alpha-tubulin. This binding site included residues that were mutated in several resistant lines. Moreover, parallel analysis of Bos taurus alpha-tubulin indicated that oryzalin did not interact with this site and had a significantly decreased, nonspecific affinity for vertebrate alpha-tubulin. We propose that the dinitroanilines act through a novel mechanism, by disrupting M-N loop contacts. These compounds also represent the first class of drugs that act on alpha-tubulin function.

Indexed as

SulfanilamidesAmino Acid SequenceAnimalsBinding SitesCattleCoccidiostatsDinitrobenzenesMicrotubulesModels, GeneticModels, MolecularMolecular Sequence DataMutagenesisMutationPhenotypePoint MutationProtein BindingCoccidiostatsDinitrobenzenesoryzalinSulfanilamidesTubulin

Identifiers

PMID14742718
PMCPMC379290
OpenAlexW2163389258

What OpenQuestion holds

Textmetadata
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.