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Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity
The synthesis of essential amino acids in plants is pivotal for their viability and growth, and these cellular pathways are therefore targeted for the discovery of new molecules for weed control. Herein, we describe the discovery and design of small molecule inhibitors of cystathionine gamma‐synthas...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428831/ https://www.ncbi.nlm.nih.gov/pubmed/33773037 http://dx.doi.org/10.1111/pbi.13591 |
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author | Bloch, Itai Haviv, Hadar Rapoport, Irena Cohen, Elad Shushan, Rotem Shelly Ben Dotan, Nesly Sher, Inbal Hacham, Yael Amir, Rachel Gal, Maayan |
author_facet | Bloch, Itai Haviv, Hadar Rapoport, Irena Cohen, Elad Shushan, Rotem Shelly Ben Dotan, Nesly Sher, Inbal Hacham, Yael Amir, Rachel Gal, Maayan |
author_sort | Bloch, Itai |
collection | PubMed |
description | The synthesis of essential amino acids in plants is pivotal for their viability and growth, and these cellular pathways are therefore targeted for the discovery of new molecules for weed control. Herein, we describe the discovery and design of small molecule inhibitors of cystathionine gamma‐synthase, a key enzyme in the biosynthesis of methionine. Based on in silico screening and filtering of a large molecular database followed by the in vitro selection of molecules, we identified small molecules capable of binding the target enzyme. Molecular modelling of the interaction and direct biophysical binding enabled us to explore a focussed chemical expansion set of molecules characterized by an active phenyl‐benzamide chemical group. These molecules are bio‐active and efficiently inhibit the viability of BY‐2 tobacco cells and seedlings growth of Arabidopsis thaliana on agar plates. |
format | Online Article Text |
id | pubmed-8428831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84288312021-09-14 Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity Bloch, Itai Haviv, Hadar Rapoport, Irena Cohen, Elad Shushan, Rotem Shelly Ben Dotan, Nesly Sher, Inbal Hacham, Yael Amir, Rachel Gal, Maayan Plant Biotechnol J Research Articles The synthesis of essential amino acids in plants is pivotal for their viability and growth, and these cellular pathways are therefore targeted for the discovery of new molecules for weed control. Herein, we describe the discovery and design of small molecule inhibitors of cystathionine gamma‐synthase, a key enzyme in the biosynthesis of methionine. Based on in silico screening and filtering of a large molecular database followed by the in vitro selection of molecules, we identified small molecules capable of binding the target enzyme. Molecular modelling of the interaction and direct biophysical binding enabled us to explore a focussed chemical expansion set of molecules characterized by an active phenyl‐benzamide chemical group. These molecules are bio‐active and efficiently inhibit the viability of BY‐2 tobacco cells and seedlings growth of Arabidopsis thaliana on agar plates. John Wiley and Sons Inc. 2021-05-12 2021-09 /pmc/articles/PMC8428831/ /pubmed/33773037 http://dx.doi.org/10.1111/pbi.13591 Text en © 2021 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Bloch, Itai Haviv, Hadar Rapoport, Irena Cohen, Elad Shushan, Rotem Shelly Ben Dotan, Nesly Sher, Inbal Hacham, Yael Amir, Rachel Gal, Maayan Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity |
title | Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity |
title_full | Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity |
title_fullStr | Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity |
title_full_unstemmed | Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity |
title_short | Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity |
title_sort | discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428831/ https://www.ncbi.nlm.nih.gov/pubmed/33773037 http://dx.doi.org/10.1111/pbi.13591 |
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