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Structural basis for recognition of antihistamine drug by human histamine receptor.

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.

SUBMITTER: Peng X

PROVIDER: S-EPMC9569329 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Structural basis for recognition of antihistamine drug by human histamine receptor.

Peng Xueqian X Yang Linlin L Liu Zixuan Z Lou Siyi S Mei Shiliu S Li Meiling M Chen Zhong Z Zhang Haitao H

Nature communications 20221015 1

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 H<sub>3</sub>R bound to an antagonist PF-03654746 at 2.6 Å resolution. Combined with the computational and functional assays, our structure reveals binding ...[more]

PMID: 36243875

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