2YMD

Crystal structure of a mutant binding protein (5HTBP-AChBP) in complex with serotonin (5-hydroxytryptamine)

2YMD の概要

• エントリーDOI: 10.2210/pdb2ymd/pdb
• 関連するPDBエントリー: 2BR7 2BR8 2BYN 2BYP 2BYQ 2BYR 2BYS 2C9T 2UZ6 2W8F 2W8G 2WN9 2WNC 2WNJ 2WNL 2WZY 2X00 2XNT 2XNU 2XNV 2XYS 2XYT 2XZ5 2XZ6 2Y54 2Y56 2Y57 2Y58 2Y7Y 2YME 4AFO 4AFT 4AFW
• 分子名称: SOLUBLE ACETYLCHOLINE RECEPTOR, SEROTONIN, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: receptor, pentameric ligand-gated ion channel
• 由来する生物種: APLYSIA CALIFORNICA (CALIFORNIA SEA HARE)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 244930.03

構造登録者

Kesters, D.,Thompson, A.J.,Brams, M.,Elk, R.v.,Spurny, R.,Geitmann, M.,Villalgordo, J.M.,Guskov, A.,Danielson, U.H.,Lummis, S.C.R.,Smit, A.B.,Ulens, C. (登録日: 2012-10-09, 公開日: 2012-12-12, 最終更新日: 2024-11-13)

主引用文献

Kesters, D.,Thompson, A.J.,Brams, M.,Van Elk, R.,Spurny, R.,Geitmann, M.,Villalgordo, J.M.,Guskov, A.,Helena Danielson, U.,Lummis, S.C.,Smit, A.B.,Ulens, C.
Structural Basis of Ligand Recognition in 5-Ht(3) Receptors.
Embo Rep., 14:49-, 2013

PubMed Abstract: The 5-HT(3) receptor is a pentameric serotonin-gated ion channel, which mediates rapid excitatory neurotransmission and is the target of a therapeutically important class of anti-emetic drugs, such as granisetron. We report crystal structures of a binding protein engineered to recognize the agonist serotonin and the antagonist granisetron with affinities comparable to the 5-HT(3) receptor. In the serotonin-bound structure, we observe hydrophilic interactions with loop E-binding site residues, which might enable transitions to channel opening. In the granisetron-bound structure, we observe a critical cation-π interaction between the indazole moiety of the ligand and a cationic centre in loop D, which is uniquely present in the 5-HT(3) receptor. We use a series of chemically tuned granisetron analogues to demonstrate the energetic contribution of this electrostatic interaction to high-affinity ligand binding in the human 5-HT(3) receptor. Our study offers the first structural perspective on recognition of serotonin and antagonism by anti-emetics in the 5-HT(3) receptor.

PubMed: 23196367
DOI: 10.1038/EMBOR.2012.189

実験手法

X-RAY DIFFRACTION (1.96 Å)