RT Journal Article
SR Electronic
T1 On the Question: Is Acetylcholinesterase an Allosteric Protein?
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 108
OP 121
VO 6
IS 2
A1 RICHARD J. KITZ
A1 LEON M. BRASWELL
A1 SARA GINSBURG
YR 1970
UL http://molpharm.aspetjournals.org/content/6/2/108.abstract
AB Classically, neuromuscular blocking agents are considered to function as competitive inhibitors of acetylcholinesterase, i.e., to interfere with acetylcholine hydrolysis by binding to the active surface of the enzyme. This and other evidence has led to the suggestion that acetylcholinesterase may also function as the "cholinergic receptor substance." We have studied the influence of some neuromuscular blocking agents on the rate of inhibition of acetylcholinesterase by carbamate compounds (physostigmine, carbachol, neostigmine) and recovery of enzyme activity. It was found that these large, bulky drugs accelerate rather than inhibit carbamylation and decarbamylation of the active site. Under conditions in which there is no evidence of inhibition of substrate hydrolysis (active site binding), curare-like compounds accelerate the recovery of catalytic activity of neostigmineinhibited acetylcholinesterase. The values of binding constants were measured, and the effects of varying concentrations of MgCl2 and acetylcholine, different temperatures and pH, and other agents are reported. The data are interpreted as evidence for an allosteric site mechanism capable of modulating activity at the catalytic surface, presumably through conformational changes in the enzyme. ACKNOWLEDGMENT The authors wish to thank Dr. I. B. Wilson for his constructive comments.