8X5Y

CryoEM structure of the histamine H1 receptor-BRIL/Anti BRIL Fab complex with astemizole

Summary for 8X5Y

• Entry DOI: 10.2210/pdb8x5y/pdb
• EMDB information: 38075
• Descriptor: Histamine H1 receptor,Soluble cytochrome b562, 1-[(4-fluorophenyl)methyl]-N-{1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl}-1H-benzimidazol-2-amine (2 entities in total)
• Functional Keywords: gpcr, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 1
• Total formula weight: 51087.93

Authors

Wang, D.D.,Guo, Q.,Tao, Y.Y. (deposition date: 2023-11-20, release date: 2024-01-17, Last modification date: 2024-10-23)

Primary citation

Wang, D.,Guo, Q.,Wu, Z.,Li, M.,He, B.,Du, Y.,Zhang, K.,Tao, Y.
Molecular mechanism of antihistamines recognition and regulation of the histamine H 1 receptor.
Nat Commun, 15:84-84, 2024

PubMed Abstract: Histamine receptors are a group of G protein-coupled receptors (GPCRs) that play important roles in various physiological and pathophysiological conditions. Antihistamines that target the histamine H receptor (HR) have been widely used to relieve the symptoms of allergy and inflammation. Here, to uncover the details of the regulation of HR by the known second-generation antihistamines, thereby providing clues for the rational design of newer antihistamines, we determine the cryo-EM structure of HR in the apo form and bound to different antihistamines. In addition to the deep hydrophobic cavity, we identify a secondary ligand-binding site in HR, which potentially may support the introduction of new derivative groups to generate newer antihistamines. Furthermore, these structures show that antihistamines exert inverse regulation by utilizing a shared phenyl group that inserts into the deep cavity and block the movement of the toggle switch residue W428. Together, these results enrich our understanding of GPCR modulation and facilitate the structure-based design of novel antihistamines.

PubMed: 38167898
DOI: 10.1038/s41467-023-44477-4

Experimental method

ELECTRON MICROSCOPY (3 Å)