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Recent developments in structural studies on acetylcholinesterase
Author(s) -
Silman Israel,
Sussman Joel L.
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13992
Subject(s) - acetylcholinesterase , torpedo , steric effects , ligand (biochemistry) , cholinergic , chemistry , biophysics , stereochemistry , computational biology , biology , biochemistry , enzyme , neuroscience , acetylcholine receptor , receptor
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 .