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Developing anti-dehydration drugs

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Identification of SB as a selective ABA receptor agonist and structural analysis of the CsPYL1-SB-AtHAB1ΔN complex. (a) PP2C inhibition assay in the presence of 100 μM SB and the indicated ABA receptors. Values ​​represent the mean ± SD of two assays. (B) Chemical structure of SB and half-maximal inhibitory concentrations (IC50) Values ​​of ABA- or SB-dependent inhibition of ΔNHAB1 by AtPYL1, AtPYL5, and AtPYL10. (c) Inhibition of seedling establishment by 1 μM ABA and 50 to 100 μM SB in WT Col-0 and either AtPYL5- or AtPYL10-overexpressing lines. Pictures were taken on the fourth day. (Dr) Quantification of ABA- or SB-mediated inhibition of root growth in the indicated genotypes. Seedlings were grown in dishes supplemented with 0.5% dimethyl sulfoxide (DMSO) (mock), 50 μM SB, or 10 μM ABA. The values ​​are the mean ± SD of three independent experiments (n = 13 to 16). Asterisks indicate statistical significance (*s <0.05, **s <0.01, and ***s <0.001) in the student R Test compared to the corresponding DMSO-treated line. (H) Ribbon representation of the total CsPYL1-SB-AtHAB1ΔN ternary complex. Ligand (SB, QB, or ABA) binding of the ternary complex occurs in the closed configuration of the receptor that is proportional to the active site of the HAB1 phosphatase. (F) Superposition of SB and QB at the ligand-binding site of CsPYL1. The steric barrier between SO’s SB oxygen2 group and fall110 CsPYL1 is represented as red brackets. (g) Detailed section of the SB (left) and QB (right) binding sites showing the hydrogen-bonding pattern of the interactions between the ligand and the CsPYL1:HAB1 complex. credit: Science advances (2023). DOI: 10.1126/sciadv.ade9948

Abscisic acid (ABA) is a plant hormone with essential functions in plant physiology. It is involved in the processes of development, growth, and the adaptive response to stress. Thus, plant adaptation to water-deficient stress conditions can be favored by activation of this phytohormone pathway. In this project, teams led by Pedro Luis Rodríguez at IBMCP in Valencia and Armando Albert at IQRF in Madrid developed a chemical genetic method to activate this pathway in an inducible manner and without penalizing plant growth.

Based on the atomic structure of the proteins involved and using genetic engineering techniques, the CSIC researchers created a modified ABA receptor that is activated by a mimetic molecule called iSB09. According to the results of their study, now published in the journal Science advancesand plants bearing this modified receptor and treated with iSB09 show high drought tolerance.

“This combination efficiently activates the ABA pathway and generates protection by triggering plant adaptation mechanisms,” says Pedro Luis Rodríguez of IBMCP (CSIC-UPV). “Individually, the iSB09 molecule also reduces water loss via transpiration in tomato plants,” he adds.

“This is the first time that an ABA receptor has been modified in crop plants to adapt it to a molecule that mimics a plant hormone,” says Armando Albert of IQRF-CSIC. “This molecule is more stable than the ABA hormone itself, which has a short half-life and can be added at the right time to protect the plant in drought conditions,” explains the CSIC researcher.






Medicines against dehydration. Credit: UPV

According to the study, this combination makes it possible to reduce the dose of agrochemicals used on crop plants because the combination with the modified receptor enhances the effect of the molecule. “We aim to improve plant resistance to drought and even, in extreme cases, to allow them to survive until watering is restored,” reveals Pedro Luis Rodríguez. “The goal is to develop drugs against drought by applying the advanced molecular knowledge developed in the plant world,” he says.

To carry out this work, the CSIC researchers used strategies previously applied in biomedicine (known as ‘drug discovery’), but in this case, transferred to agricultural biotechnology. This method is protected by the CSIC-UPV patent, of which the Institute of Molecular and Cellular Biology of Plants is a joint centre.

According to the researchers, “The iSB09 molecule will have to pass food safety studies like any other agricultural chemical, something that the company that exploits this molecule will be responsible for. The introduction of modified receptors, like all genetic modifications, is under change. In European legislation, for example However, companies can use this approach in other countries where it is permitted.”

more information:
Jorge Lozano-Juste et al, Structure-directed engineering of a receptor agonist pair for inducible activation of the ABA adaptive response to dehydration, Science advances (2023). DOI: 10.1126/sciadv.ade9948. www.science.org/doi/10.1126/sciadv.ade9948

Provided by the University Politècnica de València

the quote: Developing Drugs Against Dehydration (2023, March 28) Retrieved March 28, 2023 from https://phys.org/news/2023-03-drugs-dopped.html

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