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Updated: Jul 6, 2025

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps
Published on: July 19, 2024
Crystal structure reveals the binding mode and selectivity of a photoswitchable ligand for the adenosine A2A receptor
Tsuyoshi Araya1, Yuya Matsuba2, Harufumi Suzuki2
1Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
Abstract:
Rational synthetic expansion of photoresponsive ligands is important for photopharmacological studies. Adenosine A2A receptor (A2AR) is stimulated by adenosine and related in Parkinson's disease and other diseases. Here, we report the crystal structure of the A2AR in complex with the novel photoresponsive ligand photoNECA (blue) at 3.34 Å resolution. PhotoNECA (blue) was designed for this structural study and the cell-based assay showed a photoresponsive and receptor selective characteristics of photoNECA (blue) for A2AR. The crystal structure explains the binding mode, photoresponsive mechanism and receptor selectivity of photoNECA (blue). Our study would promote not only the rational design of photoresponsive ligands but also dynamic structural studies of A2AR.
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