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Structural basis for recognition of antihistamine drug by human histamine receptor

Author

Listed:
  • Xueqian Peng

    (Zhejiang University)

  • Linlin Yang

    (Zhengzhou University)

  • Zixuan Liu

    (Zhejiang University)

  • Siyi Lou

    (Zhejiang University)

  • Shiliu Mei

    (Zhejiang University)

  • Meiling Li

    (Zhengzhou University)

  • Zhong Chen

    (Zhejiang Chinese Medical University)

  • Haitao Zhang

    (Zhejiang University
    Zhejiang University School of Medicine)

Abstract

The histamine receptors belong to the G protein-coupled receptor (GPCR) superfamily, and play important roles in the regulation of histamine and other neurotransmitters in the central nervous system, as potential targets for the treatment of neurologic and psychiatric disorders. Here we report the crystal structure of human histamine receptor H3R bound to an antagonist PF-03654746 at 2.6 Å resolution. Combined with the computational and functional assays, our structure reveals binding modes of the antagonist and allosteric cholesterol. Molecular dynamic simulations and molecular docking of different antihistamines further elucidate the conserved ligand-binding modes. These findings are therefore expected to facilitate the structure-based design of novel antihistamines.

Suggested Citation

  • Xueqian Peng & Linlin Yang & Zixuan Liu & Siyi Lou & Shiliu Mei & Meiling Li & Zhong Chen & Haitao Zhang, 2022. "Structural basis for recognition of antihistamine drug by human histamine receptor," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33880-y
    DOI: 10.1038/s41467-022-33880-y
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    1. Dohyun Im & Jun-ichi Kishikawa & Yuki Shiimura & Hiromi Hisano & Akane Ito & Yoko Fujita-Fujiharu & Yukihiko Sugita & Takeshi Noda & Takayuki Kato & Hidetsugu Asada & So Iwata, 2023. "Structural insights into the agonists binding and receptor selectivity of human histamine H4 receptor," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Ruixue Xia & Shuang Shi & Zhenmei Xu & Henry F. Vischer & Albert D. Windhorst & Yu Qian & Yaning Duan & Jiale Liang & Kai Chen & Anqi Zhang & Changyou Guo & Rob Leurs & Yuanzheng He, 2024. "Structural basis of ligand recognition and design of antihistamines targeting histamine H4 receptor," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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