Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates
Developmental responses to auxin are regulated by facilitated uptake and efflux, but detailed molecular understanding of the carrier proteins is incomplete. We have used pharmacological tools to explore the chemical space that defines substrate preferences for the auxin uptake carrier AUX1. Total an...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
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Wiley
2017
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| Online Access: | https://eprints.nottingham.ac.uk/48440/ |
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| author | Hoyerova, Klara Hosek, Petr Quareshy, Mussa Li, Jun Klima, Petr Kubes, Martin Yemm, Antony A. Neve, Paul Tripathi, Ashutosh Bennett, Malcolm J. Napier, Richard M. |
| author_facet | Hoyerova, Klara Hosek, Petr Quareshy, Mussa Li, Jun Klima, Petr Kubes, Martin Yemm, Antony A. Neve, Paul Tripathi, Ashutosh Bennett, Malcolm J. Napier, Richard M. |
| author_sort | Hoyerova, Klara |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Developmental responses to auxin are regulated by facilitated uptake and efflux, but detailed molecular understanding of the carrier proteins is incomplete. We have used pharmacological tools to explore the chemical space that defines substrate preferences for the auxin uptake carrier AUX1. Total and partial loss-of-function aux1 mutants were assessed against wild-type for dose dependent resistance to a range of auxins and analogues. We then developed an auxin accumulation assay with associated mathematical modelling to enumerate accurate IC50 values for a small library of auxin analogues. The structure activity relationship data was analysed using molecular field analyses to create a pharmacophoric atlas of AUX1 substrates. The uptake carrier exhibits a very high level of selectivity towards small substrates including the natural indole-3-acetic acid, and the synthetic auxin 2,4-dichlorophenoxyacetic acid. No AUX1 activity was observed for herbicides based on benzoic acid (dicamba), pyridinyloxyacetic acid (triclopyr), or the 6-arylpicolinates (halauxifen), and very low affinity was found for picolinic acid-based auxins (picloram) and quinolinecarboxylic acids (quinclorac). The atlas demonstrates why some widely used auxin herbicides are not, or are very poor substrates. We list molecular descriptors for AUX1 substrates and discuss our findings in terms of herbicide resistance management. |
| first_indexed | 2025-11-14T20:09:02Z |
| format | Article |
| id | nottingham-48440 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:09:02Z |
| publishDate | 2017 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-484402020-05-04T19:23:31Z https://eprints.nottingham.ac.uk/48440/ Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates Hoyerova, Klara Hosek, Petr Quareshy, Mussa Li, Jun Klima, Petr Kubes, Martin Yemm, Antony A. Neve, Paul Tripathi, Ashutosh Bennett, Malcolm J. Napier, Richard M. Developmental responses to auxin are regulated by facilitated uptake and efflux, but detailed molecular understanding of the carrier proteins is incomplete. We have used pharmacological tools to explore the chemical space that defines substrate preferences for the auxin uptake carrier AUX1. Total and partial loss-of-function aux1 mutants were assessed against wild-type for dose dependent resistance to a range of auxins and analogues. We then developed an auxin accumulation assay with associated mathematical modelling to enumerate accurate IC50 values for a small library of auxin analogues. The structure activity relationship data was analysed using molecular field analyses to create a pharmacophoric atlas of AUX1 substrates. The uptake carrier exhibits a very high level of selectivity towards small substrates including the natural indole-3-acetic acid, and the synthetic auxin 2,4-dichlorophenoxyacetic acid. No AUX1 activity was observed for herbicides based on benzoic acid (dicamba), pyridinyloxyacetic acid (triclopyr), or the 6-arylpicolinates (halauxifen), and very low affinity was found for picolinic acid-based auxins (picloram) and quinolinecarboxylic acids (quinclorac). The atlas demonstrates why some widely used auxin herbicides are not, or are very poor substrates. We list molecular descriptors for AUX1 substrates and discuss our findings in terms of herbicide resistance management. Wiley 2017-12-19 Article PeerReviewed Hoyerova, Klara, Hosek, Petr, Quareshy, Mussa, Li, Jun, Klima, Petr, Kubes, Martin, Yemm, Antony A., Neve, Paul, Tripathi, Ashutosh, Bennett, Malcolm J. and Napier, Richard M. (2017) Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates. New Phytologist, 217 (4). pp. 1625-1639. ISSN 1469-8137 Auxin transport cheminformatics herbicide herbicide resistance molecular field maps pharmacophore structure-activity relationship uptake carrier http://onlinelibrary.wiley.com/doi/10.1111/nph.14950/full doi:10.1111/nph.14950 doi:10.1111/nph.14950 |
| spellingShingle | Auxin transport cheminformatics herbicide herbicide resistance molecular field maps pharmacophore structure-activity relationship uptake carrier Hoyerova, Klara Hosek, Petr Quareshy, Mussa Li, Jun Klima, Petr Kubes, Martin Yemm, Antony A. Neve, Paul Tripathi, Ashutosh Bennett, Malcolm J. Napier, Richard M. Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates |
| title | Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates |
| title_full | Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates |
| title_fullStr | Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates |
| title_full_unstemmed | Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates |
| title_short | Auxin molecular field maps define AUX1 selectivity: many auxin herbicides are not substrates |
| title_sort | auxin molecular field maps define aux1 selectivity: many auxin herbicides are not substrates |
| topic | Auxin transport cheminformatics herbicide herbicide resistance molecular field maps pharmacophore structure-activity relationship uptake carrier |
| url | https://eprints.nottingham.ac.uk/48440/ https://eprints.nottingham.ac.uk/48440/ https://eprints.nottingham.ac.uk/48440/ |