Pavlic M R
Arch Biochem Biophys. 1987 Mar;253(2):446-52. doi: 10.1016/0003-9861(87)90198-6.
The aim of the work was to elucidate the role of water in the reaction between acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) and methanesulfonyl fluoride, accelerated by accelerators. The reaction between the enzyme and methanesulfonyl fluoride in the presence of individual monovalent cations of the Hofmeister series was investigated. The results obtained were analyzed in comparison with the effect of methanesulfonylation of the specific accelerators tetramethylammonium and tetraethylammonium under various experimental conditions. The monovalent cations of the Hofmeister series accelerate the reaction. Their effect--as well as that of specific accelerators--significantly correlates with the effect of these agents on the structure of water. These findings, together with others, led to the following model of the role of hydration water in acylation of acetylcholinesterase. The accelerator, which may also be the cationic head of the natural substrate, binds to the anionic site of the enzyme and reduces the hydration of the nucleophilic serine -OH in the esteratic site, thus enhancing the nucleophilicity of -OH. This results in an improvement of the binding between the acylating agent and the esteratic site of acetylcholinesterase.
这项工作的目的是阐明水在由促进剂加速的乙酰胆碱酯酶（乙酰胆碱水解酶，EC 3.1.1.7）与甲磺酰氟之间反应中的作用。研究了在霍夫迈斯特系列的各个单价阳离子存在下酶与甲磺酰氟之间的反应。将所得结果与特定促进剂四甲基铵和四乙铵在各种实验条件下甲磺酰化的效果进行比较分析。霍夫迈斯特系列的单价阳离子加速该反应。它们的作用以及特定促进剂的作用与这些试剂对水结构的影响显著相关。这些发现与其他发现一起，得出了关于水合水在乙酰胆碱酯酶酰化作用中作用的如下模型。促进剂，其也可能是天然底物的阳离子头部，与酶的阴离子位点结合，并减少酯解位点中亲核性丝氨酸-OH的水合作用，从而增强-OH的亲核性。这导致酰化剂与乙酰胆碱酯酶酯解位点之间的结合得到改善。
