Recent developments in structural studies on acetylcholinesterase

Abstract

This review focuses on several recent developments concerning structure-function relationships in vertebrate acetylcholinesterase. These include studies on high-resolution structures of human acetylcholinesterase and its complexes; the first crystal structure of a snake venom acetylcholinesterase, in which open and closed states of the 'back door' are visualized; a powerful algorithm for redesigning proteins for enhanced expression in prokaryotic systems, as applied to human acetylcholinesterase, which has hitherto been an intractable target; in situ implementation of 'click chemistry' in crystalline acetylcholinesterase, which yields novel insights into the steric and dynamic changes involved in the reaction within the active-site gorge; and a study that demonstrates the effect of crystallization conditions on ligand alignment within a protein complex, in this case the methylene blue-Torpedo californica acetylcholinesterase complex, which highlights the relevance of the precipitant employed to structure-based drug design. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.

A molecular approach to rationally constructing specific fluorogenic substrates for the detection of acetylcholinesterase activity in live cells, mice brains and tissues

“…[1][2][3] AChE has been considered as the main cause of neurological disorders such as Alzheimer's disease and Parkinson's disease. [4][5][6] Abnormal alterations in AChE activity may directly inuence the function of the nervous system. [6][7][8][9] Thus, specic detection of AChE activity is still of great importance to better elucidate the function of AChE in complicated living systems, AChE-related diagnoses, and drug discovery.…”

“…[4][5][6] Abnormal alterations in AChE activity may directly inuence the function of the nervous system. [6][7][8][9] Thus, specic detection of AChE activity is still of great importance to better elucidate the function of AChE in complicated living systems, AChE-related diagnoses, and drug discovery. [9][10][11][12] Currently, several analytical methods based on colorimetric assays, 10,11 chemiluminescence, 12 electrochemical sensors, 13,14 nanoparticles, 15 and supramolecular assemblies, 16 have been engineered to probe AChE activity.…”

Synthesis of thiazolidin-4-ones and thiazinan-4-ones from 1-(2-aminoethyl)pyrrolidine as acetylcholinesterase inhibitors

“…Possibly this is due to the very high functional and structural similarity of AChE from different species including human- and rat AChE. This similarity is partly due to the equality found in the primary and tertiary structure of AChE 35 , 36 . Wiesner et al 36 .…”

The effects of acutely and subchronically applied DL-methionine on plasma oxidative stress markers and activity of acetylcholinesterase in rat cardiac tissue

“…Acetylcholinesterase (AChE) is a serine hydrolase that cleaves and inactivates the neurotransmitter acetylcholine (Ach) [17][18][19] . Although this enzyme is mostly present in the brain and sceletal muscle, it has a significant role in cholinergic system of the heart.…”