Sugar nucleotidyl transferases (SNTs) catalyze nucleotidyltransfer reactions to form sugar-nucleotides and pyrophosphate in the presence of two Mg2+ ions (Mg2+A and Mg2+B). 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 Mg2+ ions in catalyzing the reaction. Of great significance, we are able to compare the free energy barrier for the reaction with that for the Mg2+-assisted release of the product (i.e., pyrophosphate) into the solution, shedding light on the general mechanistic and kinetic aspects of catalysis by SNTs.

中文翻译：

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核苷酸转移反应机制及Mg2+离子在糖核苷酸转移酶中的作用

在两种 Mg2+ 离子（Mg2+A 和 Mg2+B）存在的情况下，糖核苷酸转移酶 (SNT) 催化核苷酸转移反应形成糖核苷酸和焦磷酸盐。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，揭示了称为 GlmU 的 SNT 中核苷酸转移反应的机制和自由能学。该研究确定了活性位点残基和 Mg2+ 离子在催化反应中的作用。具有重要意义的是，我们能够将反应的自由能垒与 Mg2+ 辅助将产物（即焦磷酸盐）释放到溶液中的自由能垒进行比较，从而阐明 SNT 催化的一般机制和动力学方面。