ArticleProceedings of the National Academy of Sciences of the United States of America2022
Chemical genetic screening identifies nalacin as an inhibitor of GH3 amido synthetase for auxin conjugation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 28 citations in OpenAlex.
- Phenylacetic acid metabolism in land plants: novel pathways and metabolites.Journal of experimental botany · 2025Article
- 6-Hydroxynicotinic Acid From Cucumis melo Inhibits Prehaustorium Formation in Phelipanche aegyptiaca via Disruption of Auxin Signalling Pathway.Molecular plant pathology · 2025Article
- Engineering saline-alkali-tolerant apple rootstock by knocking down MdGH3 genes in M9-T337.Stress biology · 2025Article
- A high-throughput differential chemical genetic screen uncovers genotype-specific compounds altering plant growth.iScience · 2025Article
- Inactivation of GH3.5 by COP1-mediated K63-linked ubiquitination promotes seedling hypocotyl elongation.Nature communications · 2025Article
- Transcriptome analysis reveals defense responses of alfalfa seedling roots toFrontiers in plant science · 2025Article
- Structure-based virtual screening identifies small-molecule inhibitors of O-fucosyltransferase SPINDLY in Arabidopsis.The Plant cell · 2024Article
- The Roles of GRETCHEN HAGEN3 (GH3)-Dependent Auxin Conjugation in the Regulation of Plant Development and Stress Adaptation.Plants (Basel, Switzerland) · 2023Review
- Precise Regulation of the TAA1/TAR-YUCCA Auxin Biosynthesis Pathway in Plants.International journal of molecular sciences · 2023Review
- New Wine in an Old Bottle: Utilizing Chemical Genetics to Dissect Apical Hook Development.Life (Basel, Switzerland) · 2022Review
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Authors and funding
21 authors at 4 institutions in 3 countries.
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Abstract
Auxin inactivation is critical for plant growth and development. To develop plant growth regulators functioning in auxin inactivation pathway, we performed a phenotype-based chemical screen in Arabidopsis and identified a chemical, nalacin, that partially mimicked the effects of auxin. Genetic, pharmacological, and biochemical approaches demonstrated that nalacin exerts its auxin-like activities by inhibiting indole-3-acetic acid (IAA) conjugation that is mediated by Gretchen Hagen 3 (GH3) acyl acid amido synthetases. The crystal structure of Arabidopsis GH3.6 in complex with D4 (a derivative of nalacin) together with docking simulation analysis revealed the molecular basis of the inhibition of group II GH3 by nalacin. Sequence alignment analysis indicated broad bioactivities of nalacin and D4 as inhibitors of GH3s in vascular plants, which were confirmed, at least, in tomato and rice. In summary, our work identifies nalacin as a potent inhibitor of IAA conjugation mediated by group II GH3 that plays versatile roles in hormone-regulated plant development and has potential applications in both basic research and agriculture.
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