Acetylcholinesterase peripheral anionic site

Bourne, Y., Taylor, P., Radic, Z., March-ot, P. Structural Insights into Ligand Interactions at the Acetylcholinesterase Peripheral Anionic Site. EMBO J. 2003, 22, 1-12. 

Johnson, G., Moore, S.W. (2003). Human acetylcholinesterase binds to mouse laminin-1 and human collagen IV by an electrostatic mechanism at the peripheral anionic site. Neuro-sci. Lett. 337 37-40. 

Lin G, Lai CY, Liao WC. Molecular recognition by acetylcholinesterase at the peripheral anionic site Structure-activity relationships for inhibitions by aryl carbamates. Bioorg Med Chem 1999 7 2683-9. 

A series of novel l, 3-dihydroxyxanthone Mannich base derivatives were synthesized, structure elucidated, and evaluated for anticholinesterase activity. Most of the target compounds exhibited moderate to good inhibitory activities with the IC50 values at micromole level concentration against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among them, 2 - ((diethylamino )methyl) -1 -hydroxy- 3 - (3 -methylbut-2-enyloxy) -9H-xanthen-9-one showed potent inhibitory activity against AChE and the best inhibitory activity against BuChE. The Mannich base derivatives were likely to bind to the active site (AS) and the peripheral anionic site (PAS) of cholinesterases [169]. 

D. Synaptic Acetylcholinesterase and Butyrylcholinesterase Have High Homology BUT Distinct Peripheral Anionic Sites and C Termini... 

The action of OP nerve agents on the nervous system results from their effects on enzymes, particularly esterases. The most notable of these esterases is acetylcholinesterase. The active site of acetylcholinesterase comprises a catalytic triad of serine, histidine and glutamic acid residues and other important features of the enzyme are a gorge connecting the active site to the surface of the protein and a peripheral anionic site (Bourne etal., 1995,1999 Sussman etal., 1991 Thompson and Richardson, 2004), The OPs phosphy-late1 the serine hydroxyl group in the active site of the enzyme. 

John.son, G., and Moore, S, W, (1999). The adhesion function on acetylcholinesterase is located at the peripheral anionic site. Btochem. Biophys Res, Commun. 258, 758-762. 

Rl. Radio, Z., Reiner, E., and Taylor, P., Role of the peripheral anionic site on acetylcholinesterase Inhibition by substrates and coumarin derivatives. Mol. Pharmacol. 39, 98-104 (1991). 

Novel galantamine derivatives with indole moiety have exhibited an activity against acetylcholinesterase up to 95 times higher than the parent compound, with one promising lead binding in a region close to the peripheral anionic site of the enzyme, where the Q-loop of amyloid beta peptide adheres [57]. 

Taylor, R Lwebuga-Mukasa, J. Lappi, S. Rademacher, J. Propidium. Fluorescence probe for a peripheral anionic site on acetylcholinesterase. Mol. Pharmacol. 1974,10,703-708. 

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