7f61
From Proteopedia
Crystal structure of human histamine receptor H3R in complex with antagonist PF03654746
Structural highlights
FunctionHRH3_HUMAN The H3 subclass of histamine receptors could mediate the histamine signals in CNS and peripheral nervous system. Signals through the inhibition of adenylate cyclase and displays high constitutive activity (spontaneous activity in the absence of agonist). Agonist stimulation of isoform 3 neither modified adenylate cyclase activity nor induced intracellular calcium mobilization. Publication Abstract from PubMedThe 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(3)R bound to an antagonist PF-03654746 at 2.6 A 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. Structural basis for recognition of antihistamine drug by human histamine receptor.,Peng X, Yang L, Liu Z, Lou S, Mei S, Li M, Chen Z, Zhang H Nat Commun. 2022 Oct 15;13(1):6105. doi: 10.1038/s41467-022-33880-y. PMID:36243875[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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