6TOS

Crystal structure of the Orexin-1 receptor in complex with GSK1059865

6TOS の概要

• エントリーDOI: 10.2210/pdb6tos/pdb
• 関連するPDBエントリー: 6TO7 6TOD
• 分子名称: Orexin receptor type 1, [(2~{S},5~{S})-2-[[(5-bromanylpyridin-2-yl)amino]methyl]-5-methyl-piperidin-1-yl]-(3-fluoranyl-2-methoxy-phenyl)methanone, TETRAETHYLENE GLYCOL, ... (9 entities in total)
• 機能のキーワード: 7tm, gpcr, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 87949.79

構造登録者

Rappas, M.,Ali, A.,Bennett, K.A.,Brown, J.D.,Bucknell, S.J.,Congreve, M.,Cooke, R.M.,Cseke, G.,de Graaf, C.,Dore, A.S.,Errey, J.C.,Jazayeri, A.,Marshall, F.H.,Mason, J.S.,Mould, R.,Patel, J.C.,Tehan, B.G.,Weir, M.,Christopher, J.A. (登録日: 2019-12-11, 公開日: 2020-01-15, 最終更新日: 2024-11-13)

主引用文献

Rappas, M.,Ali, A.A.E.,Bennett, K.A.,Brown, J.D.,Bucknell, S.J.,Congreve, M.,Cooke, R.M.,Cseke, G.,de Graaf, C.,Dore, A.S.,Errey, J.C.,Jazayeri, A.,Marshall, F.H.,Mason, J.S.,Mould, R.,Patel, J.C.,Tehan, B.G.,Weir, M.,Christopher, J.A.
Comparison of Orexin 1 and Orexin 2 Ligand Binding Modes Using X-ray Crystallography and Computational Analysis.
J.Med.Chem., 63:1528-1543, 2020

PubMed Abstract: The orexin system, which consists of the two G protein-coupled receptors OX and OX, activated by the neuropeptides OX-A and OX-B, is firmly established as a key regulator of behavioral arousal, sleep, and wakefulness and has been an area of intense research effort over the past two decades. X-ray structures of the receptors in complex with 10 new antagonist ligands from diverse chemotypes are presented, which complement the existing structural information for the system and highlight the critical importance of lipophilic hotspots and water molecules for these peptidergic GPCR targets. Learnings from the structural information regarding the utility of pharmacophore models and how selectivity between OX and OX can be achieved are discussed.

PubMed: 31860301
DOI: 10.1021/acs.jmedchem.9b01787

実験手法

X-RAY DIFFRACTION (2.13 Å)