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Efficient product clearance through exit channels in substrate hydrolysis by acetylcholinesterase
Author(s) -
Kovach Ildiko M.,
Qian Naifeng,
Bencsura Akos
Publication year - 1994
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(94)00580-x
Subject(s) - acetylcholinesterase , chemistry , acetylcholine , aché , hydrolysis , substrate (aquarium) , biophysics , channel (broadcasting) , stereochemistry , biochemistry , enzyme , biology , computer science , telecommunications , ecology , endocrinology
The channels connecting the active site of acetylcholinesterase (AChE) to the protein exterior were mapped by computational techniques in order to find potential exit routes for charged reaction products. 3.9% of the total volume of the AChE monomer is hollow space and over 50% of the void is located in the center; it is partitioned into three chambers, a deep entry channel, below it a wide channel located in a slightly positive region of AChE and ideally suitable for the exit of negatively charged fragments and a small chamber above Trp 84 and Met 83 . The latter serve as gates for the departure of the positively charged choline product of the hydrolysis of acetylcholine into the small cavity. An efficient product clearance is a prerequisite to a very low energy pathway for the irreversible hydrolysis of acetylcholine.