Catalytic mechanism of the enzyme papain: Predictions with a hybrid quantum mechanical molecular mechanical potential
Catalytic mechanism of the enzyme papain: Predictions with a hybrid quantum mechanical molecular mechanical potential
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DOI：
10.1021/ja9711472
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发表时间：
1997-12-17
影响因子：
15
通讯作者：
Hillier, IH
中科院分区：
文献类型：
--
作者：
Harrison, MJ;Burton, NA;Hillier, IH
一个混合量子力学/分子力学的方法是用来阐明结构和能量的特点酰胺水解酶木瓜蛋白酶。的酶在稳定的硫醇盐-咪唑离子对的作用进行检查和随后的攻击的半胱氨酸阴离子和质子转移从咪唑阳离子的势能途径被确定。发现反应是协同的而不是逐步的，并定位了反应的过渡态。研究了残基突变对离子对稳定性和酰胺水解障碍的影响，发现与实验结果一致。在这项工作中，使用高层次的电子结构和半经验MO方法，与固定结构的位置和表征。重排的酶的活性位点的电子结构的变化也被认为是响应。
A hybrid quantum mechanical/molecular mechanical approach is used to elucidate structural and energetic features of amide hydrolysis by the enzyme papain. The role of the enzyme in stabilizing the thiolate-imidazolium ion pair is examined and the potential energy pathway for the subsequent attack of the cysteine anion and proton transfer from the imidazolium cation is determined. The reaction is found to be concerted rather than stepwise, and the transition state for the reaction is located. The effect of residue mutations both on the ion pair stability and on the barrier to amide hydrolysis is explored and found to be in agreement with experiment. In this work both high-level electronic structure and semiempirical MO methods are used, with location and characterization of stationary structures. Rearrangement of the enzyme in response to the changing electronic structure of the active site is also considered.