Crystal structure of fatty acid thioesterase A bound by 129 fragments provides diverse development opportunities
We have fully enabled FatA as a target for rapid, rational hit-to-lead development, with robust structural, biophysical and biochemical assays. We provide a set of fragment hits which represent diverse, novel scaffolds that both recapitulate interactions made by current herbicides, and also target novel regions within the active and dimer sites. Our fragments can be readily merged and allow for effective catalogue-based structure-activity relationship (SAR) exploration. Together these data will accelerate the development of novel, alternative herbicides to combat herbicide resistance. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Authors
- Charles W.E. Tomlinson (ORCID: https://orcid.org/0000-0002-1845-6028)
- Katherine S. England (ORCID: https://orcid.org/0000-0002-4921-7505)
- M. Fairhead (ORCID: https://orcid.org/0000-0001-5361-3933)
- Xiaomin Ni (ORCID: https://orcid.org/0000-0002-7769-8297)
- L. Koekemoer (ORCID: https://orcid.org/0000-0001-9226-9127)
- F. von Delft (ORCID: https://orcid.org/0000-0003-0378-0017)
- J.C. Aschenbrenner (ORCID: https://orcid.org/0000-0002-4318-0481)
- Nicholas P. Mulholland (ORCID: https://orcid.org/0000-0001-8836-7429)
- Laura Ortega Varga (ORCID: https://orcid.org/0000-0002-9373-6337)
- R. Chalk (ORCID: https://orcid.org/0000-0002-9942-2339)
- D. Fearon (ORCID: https://orcid.org/0000-0003-3529-7863)
- Max Winokan (ORCID: https://orcid.org/0000-0002-1318-4422)
- Matteo P. Ferla (ORCID: https://orcid.org/0000-0002-5508-4673)
- Mark Montgomery (ORCID: https://orcid.org/0000-0001-9174-8281)
- Eva Kot (ORCID: https://orcid.org/0009-0003-7867-3109)
- Patricia Helen Hollinshead
Institutions
- University of Johannesburg (ZA)
- Discovery Centre (CA)
- Diamond Light Source (GB)
- Syngenta (United Kingdom) (GB)
- Research Complex at Harwell (GB)
- Alzheimer’s Research UK (GB)
- Syngenta (Switzerland) (CH)
Publication Details
- Journal
- Pest Management Science
- Published
- 2025-09-12
- DOI
- https://doi.org/10.1002/ps.70199
- Citations
- 1
- Primary Topic
- Enzyme Structure and Function
- Type
- article
- Field-Weighted Citation Impact
- 0.52