Structural insights into melatonin receptors.

ABSTRACT: The long-anticipated high-resolution structures of the human melatonin G protein-coupled receptors MT₁ and MT₂ , involved in establishing and maintaining circadian rhythm, were obtained in complex with two melatonin analogs and two approved anti-insomnia and antidepression drugs using X-ray free-electron laser serial femtosecond crystallography. The structures shed light on the overall conformation and unusual structural features of melatonin receptors, as well as their ligand binding sites and the melatonergic pharmacophore, thereby providing insights into receptor subtype selectivity. The structures revealed an occluded orthosteric ligand binding site with a membrane-buried channel for ligand entry in both receptors, and an additional putative ligand entry path in M

SUBMITTER: Stauch B 

PROVIDER: S-EPMC7174090 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature