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Conformation of acetylcholine bound to the nicotinic acetylcholine receptor.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; September 1988, Vol. 85 Issue: 18 p6721-6725, 5p
- Publication Year :
- 1988
-
Abstract
- We report here the biologically active conformation of acetylcholine when bound to the high-affinity state of the receptor from Torpedo californica. The acetylcholine conformation was determined in the free and bound states by proton NMR two-dimensional nuclear Overhauser effects. In agreement with x-ray crystallographic data, acetylcholine in solution has an extended conformation with an average distance between the acetyl methyl and choline methyl protons of approximately equal to 5 A. When bound to the acetylcholine receptor, acetylcholine adopts a conformation where the acetyl methyl group is close (3.3 A) to the methyl groups of the choline moiety. This bent conformation places the oxygens adjacent to one another and allows the methyl groups to form an uninterrupted hydrophobic surface over the rest of the acetylcholine molecule. The significant difference between the free- and bound-state conformations implies that structure-activity studies based solely on molecular modeling strategies must be approached with caution.
Details
- Language :
- English
- ISSN :
- 00278424 and 10916490
- Volume :
- 85
- Issue :
- 18
- Database :
- Supplemental Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Periodical
- Accession number :
- ejs60450478
- Full Text :
- https://doi.org/10.1073/pnas.85.18.6721