Inhibition of strigolactone receptors by N-phenylanthranilic acid derivatives: Structural and functional insights. 2018

Cyril Hamiaux, and Revel S M Drummond, and Zhiwei Luo, and Hui Wen Lee, and Prachi Sharma, and Bart J Janssen, and Nigel B Perry, and William A Denny, and Kimberley C Snowden
From the New Zealand Institute for Plant and Food Research Limited, Private Bag 92169, Auckland 1142, New Zealand, cyril.hamiaux@plantandfood.co.nz.

The strigolactone (SL) family of plant hormones regulates a broad range of physiological processes affecting plant growth and development and also plays essential roles in controlling interactions with parasitic weeds and symbiotic fungi. Recent progress elucidating details of SL biosynthesis, signaling, and transport offers many opportunities for discovering new plant-growth regulators via chemical interference. Here, using high-throughput screening and downstream biochemical assays, we identified N-phenylanthranilic acid derivatives as potent inhibitors of the SL receptors from petunia (DAD2), rice (OsD14), and Arabidopsis (AtD14). Crystal structures of DAD2 and OsD14 in complex with inhibitors further provided detailed insights into the inhibition mechanism, and in silico modeling of 19 other plant strigolactone receptors suggested that these compounds are active across a large range of plant species. Altogether, these results provide chemical tools for investigating SL signaling and further define a framework for structure-based approaches to design and validate optimized inhibitors of SL receptors for specific plant targets.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D003198 Computer Simulation Computer-based representation of physical systems and phenomena such as chemical processes. Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D012275 Oryza A genus of grass family (Poaceae) that include several rice species. Oryza sativa,Rice,Rices
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D017360 Arabidopsis A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development. Arabidopsis thaliana,Cress, Mouse-ear,A. thaliana,A. thalianas,Arabidopses,Arabidopsis thalianas,Cress, Mouse ear,Cresses, Mouse-ear,Mouse-ear Cress,Mouse-ear Cresses,thaliana, A.,thaliana, Arabidopsis,thalianas, A.
D062367 ortho-Aminobenzoates Benzoic acids, salts, or esters that contain an amino group attached to carbon number 2 or 6 of the benzene ring structure. 2-Aminobenzoates,6-Aminobenzoates,Anthranilates,Anthranilic Acids,o-Aminobenzoates,o-Aminobenzoic Acids,ortho-Aminobenzoic Acids,6 Aminobenzoates,Acids, Anthranilic,Acids, o-Aminobenzoic,Acids, ortho-Aminobenzoic,o Aminobenzoates,o Aminobenzoic Acids,ortho Aminobenzoates,ortho Aminobenzoic Acids
D029681 Arabidopsis Proteins Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments. Arabidopsis thaliana Proteins,Thale Cress Proteins,Proteins, Arabidopsis thaliana,thaliana Proteins, Arabidopsis
D032306 Petunia A plant genus of the family SOLANACEAE. Members contain steroidal glycosides. Petunias

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