Phosphonylation and aging mechanisms of mipafox and butyrylcholinesterase:A theoretical study  

作　　者：DING Jun YAO Yuan ZHANG Hui Li ZeSheng 

机构地区：[1]College of Material Science and Engineering,Harbin University of Science and Technology,Harbin 150080,China [2]Academy of Fundamental and Interdisciplinary Sciences,Harbin Institute of Technology,Harbin 150000,China [3]Key Laboratory of Cluster Seience of Ministry of Education&School of Chemistry,Beijing Institute of Technology,Beijing 100081,China

出　　处：《Chinese Science Bulletin》2012年第34期4453-4461,共9页

基　　金：supported by the National Natural Science Foundation of China (20973077 and 20973049);the Program for New Century Excellent Talents in University (NCET);the Doctor Foundation by the Ministry of Education (20112303110005);the Foundation for the Department of Education of Heilongjiang Province (1152G010 and 11551077);the Science Fundation for Leading Experts in Academe of Harbin of China(2011RFJGS026)

摘　　要：Phosphonylation and aging processes between butyrylcholinesterase with mipafox have been studied at the B3LYP/6-311G(d,p) level of theory. The calculated results indicate that the phosphonylation process employs a two-step addition-elimination mechanism with the addition (the first step) as the rate-limiting step. Two different calculation models revealed that the catalytic triad of butyrylcholinesterase plays an important role in accelerating the reaction. This is the same mechanism as the phosphonylation reaction of acetylcholinesterase by sarin reported by Wang et al. However, the energy barrier of the rate-limiting step in the present reaction is higher than that in phosphonylation reaction of acetylcholinesterase by sarin. This indicates the differences in the phosphonylation activity of sarin and mipafox. The aging process occurs through a two-step addition-elimination mechanism similar to the phosphonylation process with the addition as the rate-limiting step. The solvent effects have been evaluated by using a CPCM model and the results show that the stationary structures and the negative charges around some important atoms involved in the two processes are not significantly different. However, the energy barrier of the phosphonylation process is remarkably decreased, revealing that this process is feasible in solution.Phosphonylation and aging processes between butyrylcholinesterase with mipafox have been studied at the B3LYP/6-311G（d,p） level of theory. The calculated results indicate that the phosphonylation process employs a two-step addition-elimination mecha- nism with the addition （the first step） as the rate-limiting step. Two different calculation models revealed that the catalytic triad of butyrylcholinesterase plays an important role in accelerating the reaction. This is the same mechanism as the phosphonylation reaction of acetylcholinesterase by satin reported by Wang et al. However, the energy barrier of the rate-limiting step in the pre- sent reaction is higher than that in phosphonylation reaction of acetylcholinesterase by sarin. This indicates the differences in the phosphonylation activity of sarin and mipafox. The aging process occurs through a two-step addition-elimination mechanism similar to the phosphonylation process with the addition as the rate-limiting step. The solvent effects have been evaluated by using a CPCM model and the results show that the stationary structures and the negative charges around some important atoms involved in the two processes are not significantly different. However, the energy barrier of the phosphonylation process is remarkably decreased, revealing that this process is feasible in solution.

关 键 词：丁酰胆碱酯酶 老化机制 乙酰胆碱酯酶 老化过程 酶反应 计算结果 消除机理 计算模型 

分 类 号：O621.25[理学—有机化学]