Evidence map›Paper›PMID 41730108›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Structural and evolutionary constraints of organophosphate resistance in dipteran carboxylesterases.

Rebecca L Frkic, Alex Giang, Sacha B Pulsford, Jian-Wei Liu, Mojtaba Esmaeily, Paul D Carr, Nicholas J Fraser, Davis Hopkins, John G Oakeshott, Philip Batterham and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Rebecca L FrkicResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0003-0071-9018
Alex GiangSchool of Biosciences/Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3052, Australia.ORCID 0000-0002-9644-1374
Sacha B PulsfordResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0001-9179-9214
Jian-Wei LiuCommonwealth Scientific and Industrial Research Organisation, Land and Water, Black Mountain Laboratories, Canberra, ACT 2600, Australia.
Mojtaba EsmaeilyResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0002-5851-4501
Paul D CarrResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
Nicholas J FraserResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0002-7326-0570
Davis HopkinsResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
John G OakeshottCommonwealth Scientific and Industrial Research Organisation, Land and Water, Black Mountain Laboratories, Canberra, ACT 2600, Australia.ORCID 0000-0001-8324-7874
Philip BatterhamSchool of Biosciences/Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC 3052, Australia.ORCID 0000-0001-9840-9119
Peter D MabbittResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.
Colin J JacksonResearch School of Chemistry, Australian National University, Canberra, ACT 2601, Australia.ORCID 0000-0001-6150-3822

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Enzymatic detoxification of organophosphate (OP) insecticides can confer resistance in some insects, yet the precise molecular basis of this trait, and how it has evolved, remains poorly understood. In certain dipteran species, a G→D mutation in the oxyanion hole of α-carboxylesterases (CBEs) enhances OP hydrolysis, yet this adaptation is not widespread despite the presence of orthologous CBEs in other insect species that are also exposed to OPs. The extent, and molecular basis, of evolutionary contingency and epistasis in this catalytic OP resistance has not been explored, and how further mutations might optimize OP detoxification in the future is not clear. Here, we systematically compare OP hydrolysis and analyze structures of CBE orthologs across several dipteran species, revealing that the success of the G137D mutation is sequence context-dependent. We employed laboratory-directed evolution to enhance OP turnover over 1,000-fold vs. the wildtype enzyme and tested these variants in transgenic

Indexed as

Carboxylic Ester HydrolasesDipteraEvolution, MolecularInsecticide ResistanceInsect ProteinsOrganophosphatesAnimalsDrosophila melanogasterHydrolysisInsecticidesModels, MolecularMutationCarboxylic Ester HydrolasesInsecticidesInsect ProteinsOrganophosphatescarboxylesteraseepistasisorganophosphatesprotein evolution

Identifiers

PMID41730108
PMCPMC12956860

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.