Chem. J. Chinese Universities ›› 2009, Vol. 30 ›› Issue (11(1)): 68.

• Articles • Previous Articles     Next Articles

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

CHEN Xin1, QIAO Qing-An1*, JIN Yue-Qing2, JING Jie1, CAI Zheng-Ting3, FENG Da-Cheng3   

  1. 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.

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

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