Abstract
Flexibility of each of five inhibitors of acetylcholinesterase (AchE) has been determined from proton NMR line width of the inhibitor methyl peak on binding to 11.8 S AchE and to 11.8 S AchE previously carbamylated or sulfonylated at the active-site serine residue. When bound to unmodified AchE, all studied inhibitors show high rotational lability. For carbamylated or sulfonylated enzyme, inhibitor flexibility decreases as inhibitor size increases. The results suggest that these inhibitors (trimethylammonium, phenyltrimethylammonium, cis-2,6-dimethylspiro(piperidine-1,1-pyrrolidinium), atropine, and eserine) bind in a spatious anionic pocket near the active-site serine residue.
ACKNOWLEDGMENT The authors wish to thank Dr. J. A. Benbasat for kinetic measurements of AchE inhibition.
- Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics
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