Cation- Interactions in Ligand Recognition by Serotonergic (5-HT3A) and Nicotinic Acetylcholine Receptors: The Anomalous Bin
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- 作者：Darren L. Beene ; Gabriel S. Brandt ; Wenge Zhong ; Niki M. Zacharias ; Henry A. Lester ; and Dennis A. Dougherty
- 刊名：Biochemistry
- 出版年：2002
- 出版时间：August 13, 2002
- 年：2002
- 卷：41
- 期：32
- 页码：10262 - 10269
- 全文大小：280K
- 年卷期：v.41,no.32(August 13, 2002)
- ISSN：1520-4995
文摘
A series of tryptophan analogues has been introduced into the binding site regions of two ionchannels, the ligand-gated nicotinic acetylcholine and serotonin 5-HT3A receptors, using unnatural aminoacid mutagenesis and heterologous expression in Xenopus oocytes. A cation-
interaction betweenserotonin and Trp183 of the serotonin channel 5-HT3AR is identified for the first time, precisely locatingthe ligand-binding site of this receptor. The energetic contribution of the observed cation- interactionbetween a tryptophan and the primary ammonium ion of serotonin is estimated to be approximately 4kcal/mol, while the comparable interaction with the quaternary ammonium of acetylcholine is approximately2 kcal/mol. The binding mode of nicotine to the nicotinic receptor of mouse muscle is examined by thesame technique and found to differ significantly from that of the natural agonist, acetylcholine.
interaction betweenserotonin and Trp183 of the serotonin channel 5-HT3AR is identified for the first time, precisely locatingthe ligand-binding site of this receptor. The energetic contribution of the observed cation- interactionbetween a tryptophan and the primary ammonium ion of serotonin is estimated to be approximately 4kcal/mol, while the comparable interaction with the quaternary ammonium of acetylcholine is approximately2 kcal/mol. The binding mode of nicotine to the nicotinic receptor of mouse muscle is examined by thesame technique and found to differ significantly from that of the natural agonist, acetylcholine.