Manojkumar T K, Cui Chunzhi, Kim Kwang S
Creative Research Initiative Center for Superfunctional Materials, Department of Chemistry, Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31, Hyojadong, Namgu, Pohang 790-784, Korea.
J Comput Chem. 2005 Apr 30;26(6):606-11. doi: 10.1002/jcc.20199.
Acylation of acetylcholine (ACh) catalyzed by acetylcholinesterase (AChE) has been studied using high-level theoretical calculations on a model system that mimics the reaction center of the enzyme, and compared with uncatalyzed acylation reaction. The geometries of all the intermediates and transition states, activation energies, and solvent effects have been calculated. The calculations predict simultaneous formation of two short-strong hydrogen bonds (SSHB) in the rate-determining transition state structures [the first SSHB involves the hydrogen atom of Ser-200 (H(s)) and another involves the hydrogen atom of His-440 (H(h))]. In the intermediate states, the H-bond corresponding to H(h) involves SSHB, whereas the one corresponding to H(s) does not.
利用对模拟该酶反应中心的模型系统进行的高水平理论计算，研究了乙酰胆碱酯酶（AChE）催化的乙酰胆碱（ACh）酰化反应，并与未催化的酰化反应进行了比较。计算了所有中间体和过渡态的几何结构、活化能以及溶剂效应。计算预测在速率决定过渡态结构中会同时形成两个短强氢键（SSHB）[第一个SSHB涉及Ser-200的氢原子（H(s)），另一个涉及His-440的氢原子（H(h)）]。在中间态，对应于H(h)的氢键涉及SSHB，而对应于H(s)的氢键则不涉及。
