Recent developments in structural studies on acetylcholinesterase

Journal of Neurochemistry
I Silman, J L Sussman

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.

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Citations

Oct 28, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Adriana M das NevesWilson Cunico
Aug 10, 2017·Journal of Neurochemistry·Marco A M PradoIsrael Silman
Mar 25, 2021·Metabolic Brain Disease·Uzma SaleemBashir Ahmad

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