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.
journal_name
Proc Natl Acad Sci U S Aauthors
Behling RW,Yamane T,Navon G,Jelinski LWdoi
10.1073/pnas.85.18.6721subject
Has Abstractpub_date
1988-09-01 00:00:00pages
6721-5issue
18eissn
0027-8424issn
1091-6490journal_volume
85pub_type
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