7F61

Crystal structure of human histamine receptor H3R in complex with antagonist PF03654746

Summary for 7F61

• Entry DOI: 10.2210/pdb7f61/pdb
• Descriptor: Histamine H3 receptor, Soluble cytochrome b562, N-ethyl-3-fluoranyl-3-[3-fluoranyl-4-(pyrrolidin-1-ylmethyl)phenyl]cyclobutane-1-carboxamide, ... (5 entities in total)
• Functional Keywords: gpcr, histamine receptor, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 62550.11

Authors

Peng, X.,Zhang, H. (deposition date: 2021-06-23, release date: 2022-10-26, Last modification date: 2024-10-23)

Primary citation

Peng, X.,Yang, L.,Liu, Z.,Lou, S.,Mei, S.,Li, M.,Chen, Z.,Zhang, H.
Structural basis for recognition of antihistamine drug by human histamine receptor.
Nat Commun, 13:6105-6105, 2022

PubMed 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 HR 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.

PubMed: 36243875
DOI: 10.1038/s41467-022-33880-y

Experimental method

X-RAY DIFFRACTION (2.6 Å)