Conformation of acetylcholine bound to the nicotinic acetylcholine receptor

R. W. Behling, T. Yamane, G. Navon, L. W. Jelinski

Research output: Contribution to journalArticlepeer-review


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 ≃5 Å. When bound to the acetylcholine receptor, acetylcholine adopts a conformation where the acetyl methyl group is close (3.3 Å) 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.

Original languageEnglish
Pages (from-to)6721-6725
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number18
StatePublished - 1988
Externally publishedYes


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