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Key active site residues in the inhibition of acetylcholinesterases by soman
Author(s) -
Qian Naifeng,
Kovach Ildiko M.
Publication year - 1993
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(93)80816-d
Subject(s) - diastereomer , chemistry , soman , active site , acetylcholinesterase , alkylation , stereochemistry , adduct , enzyme , medicinal chemistry , catalysis , organic chemistry
Molecular modeling (GEMM 7.3) and molecular mechanics calculations (YETI V 5.3) using the X‐ray coordinates for acetylcholinesterase (AChE) from Torpedo californica indicate electrostatic stabilization by the active site. Glu‐199, of the developing positive charge on the incipient carbonium ion in the dealkylation in the adducts of AChE with P S C R and PsCs diastereomers of 2‐(3,3‐dimethylbutyl) methylphosphonofluoridate (soman). His‐440 is indispensable as a general acid catalyst of C‐O bond breaking in the dealkylation reaction and that of bond breaking to the Ser γ‐O in reactivation. This demand for catalysis seems to be satisfied for the reactivation of enzyme from the P s C s , diastereomer of soman, but not from the P(S)C(R) diastereomer.