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A new model for 20-hydroxyecdysone and dibenzoylhydrazine binding: A homology modeling and docking approach

Published online by Cambridge University Press:  01 June 2000

JEAN-MARIE WURTZ
Affiliation:
Laboratoire de Biologie Structurale, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P. 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
BENOIT GUILLOT
Affiliation:
Laboratoire de Biologie Structurale, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P. 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France Present address: Laboratoire de Cristallographie et Modélisation des Matériaux Minéraux et Biologiques, Faculté des Sciences, BP 239, 54506 Vandoeuvre-Lès-Nancy Cedex, France.
JÉRÔME FAGART
Affiliation:
Laboratoire de Biologie Structurale, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P. 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
DINO MORAS
Affiliation:
Laboratoire de Biologie Structurale, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P. 163, 67404 Illkirch Cedex, C.U. de Strasbourg, France
KLAUS TIETJEN
Affiliation:
Department of Molecular Target Research, Agricultural Center Monheim, Bayer AG, D-51368 Leverkusen, Germany
MICHAEL SCHINDLER
Affiliation:
Department of Molecular Target Research, Agricultural Center Monheim, Bayer AG, D-51368 Leverkusen, Germany
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Abstract

The ecdysone receptor (ECR), a nuclear transcription factor controlling insect development, is a novel target for insecticides such as dibenzoylhydrazines with low environmental and toxicological impacts. To understand the high selectivity of such synthetic molecules toward ECR, two homology models of the Chironomus tentans ECR ligand-binding domain (LDB) have been constructed by taking as templates the known LBD crystal structures of the retinoic acid and vitamin D receptors. Docking of 20-hydroxyecdysone (20E) and dibenzoylhydrazines to the receptor suggests a novel superposition of the natural and synthetic molecules; the N-tert-butyl substituent of the dibenzoylhydrazines extends significantly beyond the 20E volume. Our ECR–LBD protein models rationalize how 20E and dibenzoylhydrazines interact with the ligand-binding pocket. The homology model complexes provide new insights that can be exploited in the rational design of new environmentally safe insecticides.

Type
Research Article
Copyright
2000 The Protein Society

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