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化学学报
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化学学报 ›› 2009, Vol. 67 ›› Issue (5): 372-380. 上一篇    下一篇

研究论文

SET区域Rubisco赖氨酸甲基化转移酶催化赖氨酸多重甲基化的量子力学研究

蒋彦可a 邹建卫*,b 卢运祥a 蒋勇军b 俞庆森a

  

  1. (a浙江大学化学系 杭州 310027)
    (b浙江大学宁波理工学院分子设计与营养工程重点实验室 宁波 315104)

  • 投稿日期:2008-04-01 修回日期:2008-09-26 发布日期:2009-03-14
  • 通讯作者: 邹建卫

Quantum Mechanical Study on Multiple Lysine Methylation Catalyzed by the SET Domain Enzyme Rubisco LSMT

Jiang, Yanke a Zou, Jianwei *,b Lu, Yunxiang a Jiang, Yongjun b Yu, Qingsen a

  

  1. (a Department of Chemistry, Zhejiang University, Hangzhou 310027)
    (b Key Laboratory for Molecular Design and Nutrition Engineering, Ningbo Institute of Technology, Zhejiang University,
    Ningbo 315104)

  • Received:2008-04-01 Revised:2008-09-26 Published:2009-03-14
  • Contact: Zou, Jianwei

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用从头计算和DFT方法计算S-腺苷甲锍氨酸多重甲基化赖氨酸的反应机理. 气相中非催化反应的能垒比较低, 反应势能剖面类似于SN2反应, 而在电介质中, 反应能垒很高. 在B3LYP/6-31G*和ONIOM (MP2: B3LYP)水平, 研究了Rubisco大亚基甲基转移酶活性位点的三个残基催化转移甲基到赖氨酸反应的过程. 在ONIOM (MP2: B3LYP)水平, 预测的反应能垒为82.8 kJ/mol, 与从实验得到的87.4 kJ/mol接近. 计算结果表明, 酶对过渡态并没有特殊的稳定作用, 主要通过为反应物提供一个没有溶剂的环境, 用临近的残基把亲电和亲核的底物连接在一起, 进而促使甲基化反应的进行.

关键词: 赖氨酸甲基化, 甲基化转移酶, S-腺苷甲锍氨酸, 洋葱算法, 从头计算

The reaction mechanism of multiple lysine methylation by S-adenosylmethionine (as modeled by sulfonium ion) has been studied by means of ab initio and DFT calculations. The barriers of uncatalyzed reaction in gas phase are somewhat lower and the reaction profile resembles typical SN2 reactions, whereas the reactions present significantly higher barriers in dielectric media. The hydrogen bond contribution of three residues in the active site of the Rubisco large subunit methyltransferases to monomethylation reaction has also been evaluated by B3LYP/6-31G* and ONIOM MP2: B3LYP calculations. At the ONIOM (MP2:B3LYP) level, the reaction barrier was predicted to be 82.8 kJ/mol, which is in excellent agreement with the activation barrier of 87.4 kJ/mol estimated from the experimental value. The enzymes can not yield special stabilization on the transition state, however they provide a solvent-free room for the substrate (sulfonium ion and amine) and can bring the nucleophile and the electrophile together through the nearby residues, therefore facilitating the methylation processes.

Key words: lysine methylation, methyltransferase, adoMet, ONIOM, ab initio