Identification of novel inhibitors of plant GH3 IAA-amido synthetases through molecular docking studies.

IF 5.4 2区 生物学 Q1 PLANT SCIENCES Physiologia plantarum Pub Date : 2024-11-01 DOI:10.1111/ppl.14612
Adrián Luque, Clara Blanes-Mira, Lara Caballero, Purificación Andrea Martínez-Melgarejo, Miriam Nicolás-Albujer, Francisco Pérez-Alfocea, Gregorio Fernández-Ballester, José Manuel Pérez-Pérez
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Abstract

Auxins play a critical role in several plant developmental processes and their endogenous levels are regulated at multiple levels. The enzymes of the GRETCHEN HAGEN 3 (GH3) protein family catalyze the conjugation of amino acids to indoleacetic acid (IAA), the major endogenous auxin. The GH3 proteins are encoded by multiple redundant genes in plant genomes, making it difficult to perform functional genetic studies to understand their role in auxin homeostasis. To address these challenges, we used a chemical approach that exploits the reaction mechanism of GH3 proteins to identify small molecule inhibitors of their activity from a defined chemical library. The study evaluated receptor-ligand complexes based on their binding energy and classified them accordingly. Docking algorithms were used to correct any deviations, resulting in a list of the most important inhibitory compounds for selected GH3 enzymes based on a normalized sum of energy. The study presents atomic details of protein-ligand interactions and quantifies the effect of several of the identified small molecule inhibitors on auxin-mediated root growth processes in Arabidopsis thaliana. The direct effect of these compounds on endogenous auxin levels was measured using appropriate auxin sensors and endogenous hormone measurements. Our study has identified novel compounds of the flavonoid biosynthetic pathway that are effective inhibitors of GH3 enzyme-mediated IAA conjugation. These compounds play a versatile role in hormone-regulated plant development and have potential applications in both basic research and agriculture.

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通过分子对接研究鉴定植物 GH3 IAA-氨基合成酶的新型抑制剂。
辅酶在多种植物发育过程中发挥着关键作用,其内源水平受到多层次的调控。GRETCHEN HAGEN 3(GH3)蛋白家族的酶催化氨基酸与吲哚乙酸(IAA)(主要的内源辅助素)的共轭。GH3 蛋白在植物基因组中由多个冗余基因编码,因此很难进行功能基因研究以了解它们在辅助素平衡中的作用。为了应对这些挑战,我们采用了一种化学方法,利用 GH3 蛋白的反应机制,从一个确定的化学库中找出抑制其活性的小分子抑制剂。该研究根据受体与配体的结合能评估了受体与配体的复合物,并对它们进行了相应的分类。利用对接算法纠正任何偏差,最终根据能量的归一化总和,列出了对选定的 GH3 酶具有最重要抑制作用的化合物清单。该研究介绍了蛋白质-配体相互作用的原子细节,并量化了几种已确定的小分子抑制剂对拟南芥中辅酶介导的根生长过程的影响。这些化合物对内源植物生长素水平的直接影响是通过适当的植物生长素传感器和内源激素测量仪测得的。我们的研究发现了黄酮类生物合成途径中的新型化合物,它们是 GH3 酶介导的 IAA 共轭的有效抑制剂。这些化合物在激素调控的植物发育过程中发挥着多方面的作用,在基础研究和农业方面都有潜在的应用前景。
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来源期刊
Physiologia plantarum
Physiologia plantarum 生物-植物科学
CiteScore
11.00
自引率
3.10%
发文量
224
审稿时长
3.9 months
期刊介绍: Physiologia Plantarum is an international journal committed to publishing the best full-length original research papers that advance our understanding of primary mechanisms of plant development, growth and productivity as well as plant interactions with the biotic and abiotic environment. All organisational levels of experimental plant biology – from molecular and cell biology, biochemistry and biophysics to ecophysiology and global change biology – fall within the scope of the journal. The content is distributed between 5 main subject areas supervised by Subject Editors specialised in the respective domain: (1) biochemistry and metabolism, (2) ecophysiology, stress and adaptation, (3) uptake, transport and assimilation, (4) development, growth and differentiation, (5) photobiology and photosynthesis.
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