Structure and Function of Ecdysone Receptors-Interactions with Ecdysteroids and Synthetic Agonists
- Author(s)
- Hill, RJ; Graham, LD; Turner, KA; Howell, L; Tohidi-Esfahani, D; Fernley, R; Grusovin, J; Ren, B; Pilling, P; Lu, L; Phan, T; Lovrecz, GO; Pollard, M; Pawlak-Skrzecz, A; Streltsov, VA; Peat, TS; Winkler, DA; Lawrence, MC;
- Journal Title
- ADVANCES IN INSECT PHYSIOLOGY, VOL 43: INSECT GROWTH DISRUPTORS
- Publication Type
- Book Chapter
- 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.
- Publisher
- ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD
- Keywords
- LIGAND-BINDING DOMAIN; RETINOID-X-RECEPTORS; NUCLEAR RECEPTOR; DIROFILARIA-IMMITIS; DROSOPHILA-MELANOGASTER; CAENORHABDITIS-ELEGANS; MOLTING HORMONE; CELL-LINE; DEVELOPMENTAL EXPRESSION; PARASITIC NEMATODE
- Research Division(s)
- Structural Biology
- Publisher's Version
- https://doi.org/10.1016/B978-0-12-391500-9.00004-8
- Terms of Use/Rights Notice
- ©2012 Elsevier Ltd. All rights reserved.
Creation Date: 2012-01-01 12:00:00