Open AccessJournal Article
On the question: is acetylcholinesterase an allosteric protein?
TLDR
Data are interpreted as evidence for an allosteric site mechanism capable of modulating activity at the catalytic surface of acetylcholinesterase, presumably through conformational changes in the enzyme.Abstract:
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.read more
Citations
More filters
Journal ArticleDOI
Regulation of allosteric membrane-bound enzymes through changes in membrane lipid compostition.
Journal ArticleDOI
Interaction of fluorescence probes with acetylcholinesterase. The site and specificity of propidium binding.
Palmer Taylor,Shelley Lappi +1 more
TL;DR: Although propidium and edrophonium associate at separate sites on acetylcholinesterase, bis-quaternary ligands where the quaternary nitrogens are separated by 14 A displace both ligands from the enzyme with equal effectiveness.
Journal ArticleDOI
The Peripheral Anionic Site of Acetylcholinesterase: Structure, Functions and Potential Role in Rational Drug Design
G Johnson,S W Moore +1 more
TL;DR: The structure and multiple functions of the peripheral anionic site of acetylcholinesterase are discussed, together with its potential as a target in rational drug design for the development of novel and improved inhibitors and of therapeutics for the treatment of neural cancers, nerve regeneration and neurodegenerative disorders such as Alzheimer's disease.
Journal ArticleDOI
Molecular Biology of Synaptic Receptors
TL;DR: Preliminary work indicates the possibility of obtaining a biophysical response to acetylcholine when the receptor proteolipid is embedded in artificial bilayered lipid membrance.
Journal ArticleDOI
Thioflavin T Is a Fluorescent Probe of the Acetylcholinesterase Peripheral Site That Reveals Conformational Interactions between the Peripheral and Acylation Sites
Giancarlo V. De Ferrari,William D. Mallender,William D. Mallender,Nibaldo C. Inestrosa,Terrone L. Rosenberry +4 more
TL;DR: Thioflavin T, a fluorophore widely used to detect amyloid structure in proteins, binds selectively to the AChE peripheral site with an equilibrium dissociation constant of 1.0 μm, providing strong evidence in support of a conformational interaction between the two A cholinesterase sites.