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Binding mode of ecdysone agonists to the receptor: comparative modeling and docking studies

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Abstract

Three-dimensional structure models of the ligand-binding domain of the ecdysone receptor of Heliothis virescens were built by the homology modeling technique from the crystal structures of nuclear receptors. Two models were created based both on known ligand-binding domain structures of the receptors with the highest sequence identity to the ecdysone receptor, and on those of steroid hormone receptors. The latter model, which was found to have better stereochemical quality and be in good agreement with the binding of the steroidal framework of the endogenous agonist 20-hydroxyecdyosone, was used for docking studies. The docking of 20-hydroxyecdysone to the receptor model revealed that the ligand molecule can interact with the receptor in a similar manner to other steroid hormone–receptor complexes. The docking of a dibenzoylhydrazine agonist, chromafenozide, was performed based on the correspondences between the molecule and 20-dydroxyecdysone expected by molecular comparison. The interactions of the ligands with the receptor in the complexes modeled were investigated and found to be consistent with known structure–activity relationships.

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Acknowledgements

We are grateful to Dr. S. Miyamoto for careful reading of the manuscript.

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Authors and Affiliations

  1. Exploratory Chemistry Research Laboratories, Sankyo Co., Ltd., 2-58 Hiromachi 1-chome, Shinagawa-ku, 140-8710, Tokyo, Japan

    Atsushi Kasuya

  2. Crop Protection Department, Sankyo Co., Ltd., 1041 Yasu, Yasu-cho, Yasu-gun, 520-2342, Shiga, Japan

    Yoshihiro Sawada, Yoshihisa Tsukamoto & Keiji Tanaka

  3. Research and Development Laboratories, Agro and Speciality Chemicals Group, Nippon Kayaku Co., Ltd., 225-1, Koshikiya Horigome, Ageo, 362-0064, Saitama, Japan

    Tetsuya Toya

  4. Agro Group, Agro and Speciality Chemicals Group, Nippon Kayaku Co., Ltd., 1-11-2, Fujimi, Chiyoda-ku, 102-8172, Tokyo, Japan

    Mikio Yanagi

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  1. Atsushi Kasuya
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  2. Yoshihiro Sawada
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  3. Yoshihisa Tsukamoto
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  4. Keiji Tanaka
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  5. Tetsuya Toya
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Correspondence to Atsushi Kasuya.

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Kasuya, A., Sawada, Y., Tsukamoto, Y. et al. Binding mode of ecdysone agonists to the receptor: comparative modeling and docking studies. J Mol Model 9, 58–65 (2003). https://doi.org/10.1007/s00894-002-0113-x

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  • DOI: https://doi.org/10.1007/s00894-002-0113-x

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