Structure and function of ecdysone receptors - interactions with ecdysteroids and synthetic agonists

Ronald J Hill, Lloyd Graham, Kathleen A Turner, Linda Howell, Donya Tohidi-Esfahani, Ross Fernley, Julian Grusovin, Bin Ren, Patricia A Pilling, Louis Lu, Tram Phan, George O Lovrecz, Matthew Pollard, Anna Pawlak-Skrzecz, Victor A Streltsov, Thomas Peat, David Alan Winkler, Michael C Lawrence

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

13 Citations (Scopus)

Abstract

The binding of ecdysteroids and the bisacylhydrazine insecticide, tebufenozide, to recombinant ecdysone receptor ligand-binding domains from pest insects points to conserved and variable features of the receptor s ligand-binding pocket. Fluorophores conjugated to the terminus of the ecdysteroid alkyl chain have surprisingly little effect on receptor binding, permitting the development of a fluorescence polarization chemical library screen that has led to the discovery of a new class of ecdysone receptor ligands, the methylene lactams. X-ray structures of ecdysone receptor ligand-binding domains have allowed identification of the conserved and variable features within the binding pocket. The structures offer explanations for the lepidopteran selectivity of the bisacylhydrazines, the effect of amino acid replacements on the binding of ecdysteroids and other chemistries, and the preference of a phytophagous pentatomomorphan for makisterone A; indeed, they speak to the control spectra of future ecdysone receptor-targeting insecticides. Possible ligands for nematode ecdysone receptor orthologs are also considered.
Original languageEnglish
Title of host publicationInsect Growth Disruptors
EditorsTarlochan S Dhadialla
Place of PublicationLondon UK
PublisherElsevier
Pages299 - 351
Number of pages53
Edition43
ISBN (Print)9780123915009
DOIs
Publication statusPublished - 2012

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