天冬氨酸酰基转移酶催化机理及其抑制剂的密度泛函理论研究

高等学校化学学报 ›› 2009, Vol. 30 ›› Issue (11(1)): 68.

天冬氨酸酰基转移酶催化机理及其抑制剂的密度泛函理论研究

陈鑫¹, 乔青安¹, 靳月庆², 荆杰¹, 蔡政亭³, 冯大诚³

1. 鲁东大学化学与材料科学学院,
2. 图书馆, 烟台 264025;
3. 山东大学理论化学研究所, 济南250100

收稿日期:2009-07-28 出版日期:2009-11-30 发布日期:2009-11-30
通讯作者: 乔青安, 女, 博士, 副教授, 主要从事理论化学计算方面研究. E-mail: qiaoqa@sdu.edu.cn; qiaoqa@hotmail.com
基金资助:
国家自然科学基金(批准号: 20603030和20873074)、山东省自然科学基金(批准号: Q2008B07)、鲁东大学青年自然科学基金(批准号: LY20082901和LY20072903)和鲁东大学科技创新团队基金(批准号: 08-CXA001)资助.

DFT Study on the Catalytic Mechanism of Aspartoacylase and Hydrolysis Pathway of the Inhibitor

CHEN Xin¹, QIAO Qing-An^1*, JIN Yue-Qing², JING Jie¹, CAI Zheng-Ting³, FENG Da-Cheng³

1. School of Chemistry and Materials Science,
2. Library of Ludong University, Ludong University, Yantai 264025, China;
3. Institute of Theoretical Chemistry, Shandong University, Jinan 250100, China

Received:2009-07-28 Online:2009-11-30 Published:2009-11-30
Contact: QIAO Qing-An. E-mail: qiaoqa@sdu.edu.cn; qiaoqa@hotmail.com
Supported by:
国家自然科学基金(批准号: 20603030和20873074)、山东省自然科学基金(批准号: Q2008B07)、鲁东大学青年自然科学基金(批准号: LY20082901和LY20072903)和鲁东大学科技创新团队基金(批准号: 08-CXA001)资助.

摘要/Abstract

摘要：

利用密度泛函理论B3LYP方法, 在6-31G*基组水平上研究了N-乙酰-L-天冬氨酸(NAA)的水解机理以及天冬氨酸酰基转移酶抑制剂N-膦酰基甲基-L-天冬氨酸(NMPA)的作用机理. 研究结果表明, 二者的动力学性质类似, 均有两条可能的路径, 即协同反应和分步反应, 后者在竞争中占优势, 是反应的主要通道. 二者不同之处在于, NMPA水解所需的活化能与NAA相比大幅度降低, 生成的中间体更为稳定, 电荷布居变化幅度更大, 反应更易进行, 因此占据活性位后可以有效地抑制NAA的水解.

关键词: 天冬氨酸酰基转移酶; N-乙酰-L-天冬氨酸; 抑制剂; 密度泛函理论

Abstract:

The hydrolysis mechanisms of N-acetyl-L-aspartate(NAA) and a potent inhibition of aspartoacylase, N-methylphosphono-L-aspartate(NMPA), were investigated by Density Functional Theory(DFT) of B3LYP method at 6-31G* basis level. The results indicated that the dynamical properties of the hydrolysis reactions for NAA and NMPA were similar. Both of them could be achieved through two possible reaction pathways: one was concerted and the other was stepwise, and the latter was the preferred on the potential energy surface. Compared with the reaction of NAA, the intermediate formed during the NMPA hydrolysis was more stable, and through which the NBO charges varied in a wider fluctuation. If NMPA occupied the active site, it could effectively inhibit the hydrolysis reaction of NAA.

Key words: Aspartoacylase; N-Acetyl-L-aspartate(NAA); Inhibitor; Density functional theory

TrendMD:

陈鑫, 乔青安, 靳月庆, 荆杰, 蔡政亭, 冯大诚. 天冬氨酸酰基转移酶催化机理及其抑制剂的密度泛函理论研究. 高等学校化学学报, 2009, 30(11(1)): 68.

CHEN Xin, QIAO Qing-An*, JIN Yue-Qing, JING Jie, CAI Zheng-Ting, FENG Da-Cheng. DFT Study on the Catalytic Mechanism of Aspartoacylase and Hydrolysis Pathway of the Inhibitor. Chem. J. Chinese Universities, 2009, 30(11(1)): 68.

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