A Stereochemical Test of a Proposed Structural Feature of the Nicotinic Acetylcholine Receptor
| Autor: | Ariele P. Hanek, Henry A. Lester, Dennis A. Dougherty |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Stereochemistry Stereoisomerism General Chemistry Gating Receptors Nicotinic Biochemistry Catalysis Protein Subunits chemistry.chemical_compound Nicotinic acetylcholine receptor Colloid and Surface Chemistry chemistry Mutation Side chain Epimer Threonine Isoleucine Protein Structure Quaternary Caltech Library Services Methyl group |
| Zdroj: | Journal of the American Chemical Society. 130:13216-13218 |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Understanding the gating mechanism of the nicotinic acetylcholine receptor (nAChR) and similar channels constitutes a significant challenge in chemical neurobiology. In the present work, we use a stereochemical probe to evaluate a proposed pin-into-hydrophobic socket mechanism for the alphaVal46 side chain of the nAChR. Utilizing nonsense suppression methodology we incorporated isoleucine (Ile), O-methyl threonine (Omt) and threonine (Thr) as well as their side chain epimers (the allo counterparts). Surprisingly, our results indicate that only the pro-S methyl group of the alphaVal46 side chain is sensitive to changes in hydrophobicity, consistent with the precise geometrical requirements of the pin-into-socket mechanism. |
| Databáze: | OpenAIRE |
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