title: Key active site residues in the inhibition of acetylcholinesterases by soman.
abstract: 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 PSCR 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 gamma-O in reactivation. This demand for catalysis seems to be satisfied for the reactivation of enzyme from the PSCS diastereomer of soman, but not from the P(S)C(R) diastereomer.
authors.affiliation: Department of Chemistry, Catholic University of America, Washington, DC 20064.
authors.forename: N
authors.initials: N
authors.lastname: Qian
authors.forename: I M
authors.initials: IM
authors.lastname: Kovach
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012999:Soman / Q000494:pharmacology*; D014101:Torpedo; D014961:X-Ray Diffraction
chemical_list: D002800:Cholinesterase Inhibitors; D012999:Soman; D000110:Acetylcholinesterase