6BQG

Crystal structure of 5-HT2C in complex with ergotamine

6BQG の概要

• エントリーDOI: 10.2210/pdb6bqg/pdb
• 分子名称: 5-hydroxytryptamine receptor 2C,Soluble cytochrome b562, Ergotamine, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate (3 entities in total)
• 機能のキーワード: human 5-ht2c receptor, gpcr, ergotamine, polypharmacology, bril, lcp, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Cell membrane ; Multi-pass membrane protein : P28335
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 52248.26

構造登録者

Peng, Y.,McCorvy, J.D.,Harpsoe, K.,Lansu, K.,Yuan, S.,Popov, P.,Qu, L.,Pu, M.,Che, T.,Nikolajse, L.F.,Huang, X.P.,Wu, Y.,Shen, L.,Bjorn-Yoshimoto, W.E.,Ding, K.,Wacker, D.,Han, G.W.,Cheng, J.,Katritch, V.,Jensen, A.A.,Hanson, M.A.,Zhao, S.,Gloriam, D.E.,Roth, B.L.,Stevens, R.C.,Liu, Z. (登録日: 2017-11-27, 公開日: 2018-02-14, 最終更新日: 2024-10-30)

主引用文献

Peng, Y.,McCorvy, J.D.,Harpsoe, K.,Lansu, K.,Yuan, S.,Popov, P.,Qu, L.,Pu, M.,Che, T.,Nikolajsen, L.F.,Huang, X.P.,Wu, Y.,Shen, L.,Bjorn-Yoshimoto, W.E.,Ding, K.,Wacker, D.,Han, G.W.,Cheng, J.,Katritch, V.,Jensen, A.A.,Hanson, M.A.,Zhao, S.,Gloriam, D.E.,Roth, B.L.,Stevens, R.C.,Liu, Z.J.
5-HT2C Receptor Structures Reveal the Structural Basis of GPCR Polypharmacology.
Cell, 172:719-730.e14, 2018

PubMed Abstract: Drugs frequently require interactions with multiple targets-via a process known as polypharmacology-to achieve their therapeutic actions. Currently, drugs targeting several serotonin receptors, including the 5-HT receptor, are useful for treating obesity, drug abuse, and schizophrenia. The competing challenges of developing selective 5-HT receptor ligands or creating drugs with a defined polypharmacological profile, especially aimed at G protein-coupled receptors (GPCRs), remain extremely difficult. Here, we solved two structures of the 5-HT receptor in complex with the highly promiscuous agonist ergotamine and the 5-HT receptor-selective inverse agonist ritanserin at resolutions of 3.0 Å and 2.7 Å, respectively. We analyzed their respective binding poses to provide mechanistic insights into their receptor recognition and opposing pharmacological actions. This study investigates the structural basis of polypharmacology at canonical GPCRs and illustrates how understanding characteristic patterns of ligand-receptor interaction and activation may ultimately facilitate drug design at multiple GPCRs.

PubMed: 29398112
DOI: 10.1016/j.cell.2018.01.001

実験手法

X-RAY DIFFRACTION (3 Å)