Nicotinic Agonist Binding Site Mapped by Methionine- and Tyrosine-Scanning Coupled with Azidochloropyridinyl Photoaffinity Labeling
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- 作者：Motohiro Tomizawa ; Todd T. Talley ; John F. Park ; David Maltby ; Katalin F. Medzihradszky ; Kathleen A. Durkin ; Jose M. Cornejo-Bravo ; Alma L. Burlingame ; John E. Casida ; Palmer Taylor
- 刊名：Journal of Medicinal Chemistry
- 出版年：2009
- 出版时间：June 25, 2009
- 年：2009
- 卷：52
- 期：12
- 页码：3735-3741
- 全文大小：217K
- 年卷期：v.52,no.12(June 25, 2009)
- ISSN：1520-4804
文摘
Agonists activating nicotinic acetylcholine receptors (nAChR) include potential therapeutic agents and also toxicants such as epibatidine and neonicotinoid insecticides with a chloropyridinyl substituent. Nicotinic agonist interactions with mollusk (Aplysia californica) acetylcholine binding protein, a soluble surrogate of the nAChR extracellular domain, are precisely defined by scanning with 17 methionine and tyrosine mutants within the binding site by photoaffinity labeling with 5-azido-6-chloropyridin-3-yl probes that have similar affinities to their nonazido counterparts. Methionine and tyrosine are the only residues found derivatized, and their reactivity exquisitely depends on the direction of the azido moiety and its apposition to the reactive amino acid side chains.