9EHS

Structure of a human adenosine A3 receptor complex bound to the covalent antagonist LUF7602

これはPDB形式変換不可エントリーです。

9EHS の概要

• エントリーDOI: 10.2210/pdb9ehs/pdb
• EMDBエントリー: 48065
• 分子名称: BAG2 Anti-BRIL Fab Heavy Chain, elbow nanobody, BAG2 Anti-BRIL Fab Light Chain, ... (5 entities in total)
• 機能のキーワード: g protein-coupled receptor, adenosine binding, seven transmembrane protein, membrane protein, signaling protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 116745.63

構造登録者

Zhang, L.,Mobbs, J.I.,Glukhova, A.,Thal, D.M. (登録日: 2024-11-24, 公開日: 2025-08-20, 最終更新日: 2025-09-03)

主引用文献

Zhang, L.,Mobbs, J.I.,Bennetts, F.M.,Venugopal, H.,Nguyen, A.T.N.,Christopoulos, A.,van der Es, D.,Heitman, L.H.,May, L.T.,Glukhova, A.,Thal, D.M.
Molecular basis of ligand binding and receptor activation at the human A 3 adenosine receptor.
Nat Commun, 16:7674-7674, 2025

PubMed Abstract: Adenosine receptors (ARs: AAR, AAR, AAR, and AAR) are crucial therapeutic targets; however, developing selective, efficacious drugs for them remains a significant challenge. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of the human AAR in three distinct functional states: bound to the endogenous agonist adenosine, the clinically relevant agonist Piclidenoson, and the covalent antagonist LUF7602. These structures, complemented by mutagenesis and pharmacological studies, reveal an AAR activation mechanism that involves an extensive hydrogen bond network from the extracellular surface down to the orthosteric binding site. In addition, we identify a cryptic pocket that accommodates the N-iodobenzyl group of Piclidenoson through a ligand-dependent conformational change of M174. Our comprehensive structural and functional characterisation of AAR advances our understanding of adenosine receptor pharmacology and establishes a foundation for developing more selective therapeutics for various disorders, including inflammatory diseases, cancer, and glaucoma.

PubMed: 40825947
DOI: 10.1038/s41467-025-62872-x

実験手法

ELECTRON MICROSCOPY (3.2 Å)