Vishveshwara S, Madhusudhan M S, Maizel J V
Molecular Biophysics Unit, Indian Institute of Science, Bangalore.
Biophys Chem. 2001 Feb 15;89(2-3):105-17. doi: 10.1016/s0301-4622(00)00221-0.
There is growing evidence that some enzymes catalyze reactions through the formation of short-strong hydrogen bonds as first suggested by Gerlt and Gassman. Support comes from several experimental and quantum chemical studies that include correlation energies on model systems. In the present study, the process of proton transfer between hydroxyl and imidazole groups, a model of the crucial step in the hydrolysis of RNA by the enzymes of the RNase A family, is investigated at the quantum mechanical level of density functional theory and perturbation theory at the MP2 level. The model focuses on the nature of the formation of a complex between the important residues of the protein and the hydroxyl group of the substrate. We have also investigated different configurations of the ground state that are important in the proton transfer reaction. The nature of bonding between the catalytic unit of the enzyme and the substrate in the model is investigated by Bader's atoms in molecule theory. The contributions of solvation and vibrational energies corresponding to the reactant, the transition state and the product configurations are also evaluated. Furthermore, the effect of protein environment is investigated by considering the catalytic unit surrounded by complete proteins--RNase A and Angiogenin. The results, in general, indicate the formation of a short-strong hydrogen bond and the formation of a low barrier transition state for the proton transfer model of the enzyme.
越来越多的证据表明，正如格尔特（Gerlt）和加斯曼（Gassman）最初所提出的那样，一些酶通过形成短而强的氢键来催化反应。这一观点得到了多项实验和量子化学研究的支持，这些研究包括对模型系统的相关能量计算。在本研究中，我们在密度泛函理论的量子力学水平以及MP2水平的微扰理论下，研究了羟基和咪唑基团之间的质子转移过程，这是核糖核酸酶A家族的酶催化RNA水解关键步骤的一个模型。该模型聚焦于蛋白质重要残基与底物羟基形成复合物的本质。我们还研究了在质子转移反应中重要的基态的不同构型。通过巴德（Bader）的分子中的原子理论研究了模型中酶的催化单元与底物之间的键合本质。同时也评估了与反应物、过渡态和产物构型相对应的溶剂化和振动能量的贡献。此外，通过考虑被完整蛋白质（核糖核酸酶A和血管生成素）包围的催化单元，研究了蛋白质环境的影响。总体而言，结果表明形成了短而强的氢键，并且该酶的质子转移模型形成了低势垒过渡态。
