PG binds to specific receptors and is involved in a wide range of reactions, from local reactions such as redness, warmth, swelling, and pain in acute inflammation to systemic reactions such as fever, malaise, and loss of appetite.Non-steroidal anti-inflammatory drugs such as aspirin exert their effects by inhibiting the biosynthesis of a series of PGs, which are bioactive substances, by inhibiting PG synthase.In recent years, attention has been paid to the chronic inflammatory action of PG and its action on cancer, and basic research has reported that aspirin has an inhibitory effect on the onset and progression of various cancers.Currently, the development of a selective drug "super aspirin" that promotes the good action of PG based on the receptor and suppresses the bad action is expected.

　In the study, insect cells were first used to express large amounts of PGE2 receptors (EP3 and EP4), which are one of the PGs.Next, for EP4, an antibody that inhibits the PGE2-EP4 signal was bound to EP4 and crystallized using a method called the "lipid cubic phase method".Furthermore, we succeeded in improving the resolution of crystals by using the "theoretical heat resistance prediction method" developed by Kyoto University and Chiba University. The three-dimensional structure of the complex of EP4 and antibody bound to the EP4 antagonist and the three-dimensional structure of EP2 bound to PGE3 were elucidated.

　This time, the "form" of the target molecule, prostaglandin receptor, which is expected to develop many drugs, has been elucidated at the atomic level.In the future, it is expected that it will be possible to search for and design therapeutic agents that are highly effective and have few side effects for chronic inflammation, cancer, psychiatric disorders, etc. based on the three-dimensional structure.

Paper information:[Nature Chemical Biology] Ligand binding to human prostaglandin E receptor EP4 at the lipid-bilayer interface