Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India.
Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute, Mysore, India.
Biophys J. 2020 Aug 4;119(3):619-627. doi: 10.1016/j.bpj.2020.06.017. Epub 2020 Jun 24.
Sugar nucleotidyl transferases (SNTs) catalyze nucleotidyltransfer reactions to form sugar-nucleotides and pyrophosphate in the presence of two Mg ions (Mg and Mg). We unveil the mechanism and free energetics of nucleotidyl transfer reaction in an SNT called GlmU through hybrid quantum mechanics-molecular mechanics molecular dynamics simulations and free energy calculations. The study identifies the roles of the active site residues and the Mg ions in catalyzing the reaction. Of great significance, we are able to compare the free energy barrier for the reaction with that for the Mg-assisted release of the product (i.e., pyrophosphate) into the solution, shedding light on the general mechanistic and kinetic aspects of catalysis by SNTs.
糖核苷酸转移酶（SNTs）在两个镁离子（Mg 和 Mg）的存在下催化核苷酸转移反应，形成糖核苷酸和焦磷酸。我们通过混合量子力学-分子力学分子动力学模拟和自由能计算，揭示了一种名为 GlmU 的 SNT 中的核苷酸转移反应的机制和自由能。该研究确定了活性位点残基和镁离子在催化反应中的作用。重要的是，我们能够比较反应的自由能势垒与 Mg 辅助产物（即焦磷酸盐）释放到溶液中的自由能势垒，这揭示了 SNTs 催化的一般机制和动力学方面。
