News Releases & Research Results Elucidation of the structure of the dopamine receptor involved in schizophrenia - Rapid search and designing of drugs with fewer side effects -

The results of the collaborative research project conducted by Assistant Professor Im Dohyun, Professor So Iwata, and Specially Appointed Lecturer Tatsuro Shimamura of the Graduate School of Medicine, Kyoto University, Associate Professor Asuka Inoue of the Graduate School of Pharmaceutical Sciences and Professor Eriko Nango of the Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, and Group Leader Kensuke Tono of the XFEL Utilization Division, Japan Synchrotron Radiation Research Institute.

• The three-dimensional structure of the dopamine D2 receptor, which is activated by dopamine for signal transduction, was successfully elucidated using an X-ray free-electron laser (XFEL).
• The drug-binding site (pocket) on the dopamine D2 receptor might take two markedly different forms. Furthermore, a cavity peculiar to the dopamine D2 receptor was found near the pocket.
• The results of this research should promote the development of effective therapeutic agents with fewer side effects.

This project was conducted with the support of the Platform Project for Supporting Drug Discovery and Life Science Research by AMED.

The results of this research project were published in the international academic journal Nature Communications on December 22.

Dohyun Im, et al. Structure of the dopamine D2 receptor in complex with the antipsychotic drug spiperone Nature Communications
DOI: 10.1038/s41467-020-20221-0