Premium
Theoretical insights into the mechanism of acetylcholinesterase‐catalyzed acylation of acetylcholine
Author(s) -
Manojkumar T. K.,
Cui Chunzhi,
Kim Kwang S.
Publication year - 2005
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.20199
Subject(s) - acylation , chemistry , acetylcholinesterase , transition state , hydrogen atom , catalysis , acetylcholine , hydrogen bond , computational chemistry , solvent , stereochemistry , medicinal chemistry , enzyme , organic chemistry , molecule , medicine , alkyl , endocrinology
Acylation of acetylcholine (ACh) catalyzed by acetylcholinesterase (AChE) has been studied using high‐level theoretical calculations on a model system that mimics the reaction center of the enzyme, and compared with uncatalyzed acylation reaction. The geometries of all the intermediates and transition states, activation energies, and solvent effects have been calculated. The calculations predict simultaneous formation of two short‐strong hydrogen bonds (SSHB) in the rate‐determining transition state structures [the first SSHB involves the hydrogen atom of Ser‐200 (H s ) and another involves the hydrogen atom of His‐440 (H h )]. In the intermediate states, the H‐bond corresponding to H h involves SSHB, whereas the one corresponding to H s does not. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 606–611, 2005