Structural analysis of the histamine H1 receptor

Mitsunori Shiroishi, Takuya Kobayashi

研究成果: 著書/レポートタイプへの貢献

3 引用 (Scopus)

抄録

The crystal structure of the human histamine H1 receptor (H1R) has been determined in complex with its inverse agonist doxepin, a first-generation antihistamine. The crystal structure showed that doxepin sits deeply inside the ligand-binding pocket and predominantly interacts with residues highly conserved among other aminergic receptors. This binding mode is considered to result in the low selectivity of the first-generation antihistamines for H1R. The crystal structure also revealed the mechanism of receptor inactivation by the inverse agonist doxepin. On the other hand, the crystal structure elucidated the anion-binding site near the extracellular portion of the receptor. This site consists of residues not conserved among other aminergic receptors, which are specific for H1R. Docking simulation and biochemical experimentation demonstrated that a carboxyl group on the second-generation antihistamines interacts with the anion-binding site. These results imply that the anion-binding site is a key site for the development of highly selective antihistamine drugs.

元の言語英語
ホスト出版物のタイトルHandbook of Experimental Pharmacology
出版者Springer New York LLC
ページ21-30
ページ数10
DOI
出版物ステータス出版済み - 1 1 2017

出版物シリーズ

名前Handbook of Experimental Pharmacology
241
ISSN(印刷物)0171-2004
ISSN(電子版)1865-0325

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Doxepin
Histamine H1 Receptors
Histamine Antagonists
Structural analysis
Anions
Crystal structure
Binding Sites
Non-Sedating Histamine H1 Antagonists
Ligands
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

これを引用

Shiroishi, M., & Kobayashi, T. (2017). Structural analysis of the histamine H1 receptor. : Handbook of Experimental Pharmacology (pp. 21-30). (Handbook of Experimental Pharmacology; 巻数 241). Springer New York LLC. https://doi.org/10.1007/164_2016_10

Structural analysis of the histamine H1 receptor. / Shiroishi, Mitsunori; Kobayashi, Takuya.

Handbook of Experimental Pharmacology. Springer New York LLC, 2017. p. 21-30 (Handbook of Experimental Pharmacology; 巻 241).

研究成果: 著書/レポートタイプへの貢献

Shiroishi, M & Kobayashi, T 2017, Structural analysis of the histamine H1 receptor. : Handbook of Experimental Pharmacology. Handbook of Experimental Pharmacology, 巻. 241, Springer New York LLC, pp. 21-30. https://doi.org/10.1007/164_2016_10
Shiroishi M, Kobayashi T. Structural analysis of the histamine H1 receptor. : Handbook of Experimental Pharmacology. Springer New York LLC. 2017. p. 21-30. (Handbook of Experimental Pharmacology). https://doi.org/10.1007/164_2016_10
Shiroishi, Mitsunori ; Kobayashi, Takuya. / Structural analysis of the histamine H1 receptor. Handbook of Experimental Pharmacology. Springer New York LLC, 2017. pp. 21-30 (Handbook of Experimental Pharmacology).
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