Key active site residues in the inhibition of acetylcholinesterases by soman

FEBS Letters

Qian, Naifeng¹  Kovach, Ildiko M.¹ 

[1] Department of Chemistry, The Catholic University of America, Washington, DC 20064, USA

关键词: Acetylcholinesterase inhibition;    Serine hydrolase inhibition;    Irreversible enzyme inhibition;    Enzyme inhibition by organophosphorus compound;   

DOI  :  10.1016/0014-5793(93)80816-D

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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_SC_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_sC_s, diastereomer of soman, but not from the P(S)C(R) diastereomer.

【 授权许可】

Unknown