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首页> 外文期刊>The journal of physical chemistry, A. Molecules, spectroscopy, kinetics, environment, & general theory >Role of second coordination sphere amino acid residues on the proton transfer mechanism of human carbonic anhydrase II (HCA II)
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Role of second coordination sphere amino acid residues on the proton transfer mechanism of human carbonic anhydrase II (HCA II)

机译：第二配位球氨基酸残基在人类碳酸酐酶II（HCA II）的质子转移机制中的作用

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摘要

The barrier for the proton transfer in human carbonic anhydrase II (HCA II) has been studied by including the important second coordination sphere residues to the minimalistic model of the active site using B3LYP/6-31+G* level of calculation. Specifically, proton transfer from a zinc-bound water molecule to a histidine residue (His64) mediated by a water bridge (consists of two and three water molecules) has been investigated. The new model contains three functional groups of second coordination sphere residues such as Gln92, Glu117, and Asn244. These residues interact with His94, His119, and His96, respectively. We have calculated the barrier for the proton transfer using the total energies of reactants, transition states, and products. The calculated barrier height for the models with two water and three water molecules are 8.94 and 8.67 kcal/mol, respectively, which are in close agreement with the experimental value of 7.8 kcal/mol obtained from the kinetic experiments and to the range 8-10 kcal/mol predicted from the pK_a considerations (Silverman, D. N. Biochim. Biophys. Acta 2000, 1458, 88 -103.). In addition, our own N-layered integrated molecular orbital + molecular mechanics (ONIOM) calculations have also been carried out on various model systems to understand the effect of complete environment. It is possible to note from the results that the confinement of water molecules by the protein milieu appreciably decreases the O?O distance between water molecules in the water bridge when compared to the free water dimer which enables the proton transfer from one water to the other and finally to the His64 residue.
机译：通过使用计算的B3LYP / 6-31 + G *水平将重要的第二配位球残基包括在活性位点的简约模型中，已研究了人类碳酸酐酶II（HCA II）中质子转移的障碍。具体地，已经研究了由水桥介导的质子从锌结合的水分子转移至组氨酸残基（His64）（由两个和三个水分子组成）。新模型包含第二个协调球残基的三个功能组，例如Gln92，Glu117和Asn244。这些残基分别与His94，His119和His96相互作用。我们使用反应物，过渡态和产物的总能量计算了质子转移的势垒。对于具有两个水分子和三个水分子的模型，计算出的势垒高度分别为8.94和8.67 kcal / mol，与动力学实验获得的7.8 kcal / mol的实验值非常吻合，范围为8-10由pK_a考虑值预测的kcal / mol（Silverman，DN Biochim.Biophys.Acta 2000，1458，88-103。）。此外，我们还对各种模型系统进行了我们自己的N层集成分子轨道+分子力学（ONIOM）计算，以了解完整环境的影响。从结果中可能注意到，与游离水二聚体相比，通过蛋白质环境限制的水分子可显着降低水桥中水分子之间的O2O距离，从而使质子从一种水转移到另一种水最后是His64残基。

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