KEY ACTIVE-SITE RESIDUES IN THE INHIBITION OF ACETYLCHOLINESTERASES BY SOMAN

被引：37

作者：

QIAN, NF ^{[1
]}

KOVACH, IM ^{[1
]}

机构：

[1] CATHOLIC UNIV AMER, DEPT CHEM, WASHINGTON, DC 20064 USA

来源：

FEBS LETTERS | 1993年 / 336卷 / 02期

关键词：

ACETYLCHOLINESTERASE INHIBITION; SERINE HYDROLASE INHIBITION; IRREVERSIBLE ENZYME INHIBITION; ENZYME INHIBITION BY ORGANOPHOSPHORUS COMPOUND;

D O I：

10.1016/0014-5793(93)80816-D

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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(S)C(R) and P(S)C(S) diastereomers of 2-(3,3-dimethylbutyl) methylphosphonofluoridate (soman). His-440 is indispensable as a general acid catalyst of C-0 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 P(S)C(S) diastereomer of soman, but not from the P(S)C(R) diastereomer.

引用

页码：263 / 266

页数：4