Shearer Jason
Department of Chemistry/216, University of Nevada, Reno, Nevada 89557-0216, USA.
J Phys Chem B. 2008 Dec 25;112(51):16995-7002. doi: 10.1021/jp808288p.
Arginine methylation is a post-translational protein modification that is catalyzed by proteins known as arginine methyl transferases (RMTs). Recently, arginine methylation was postulated as an important modification in modulating biomolecular interactions. RMTs largely target nuclear proteins, so it is highly likely that they aid in modulating protein...DNA interactions. In this study, we probe the influence that sequential guanidinium methylation has on the energetics of the guanidinium...guanine and guanidinium...guanine...cytosine complexes using ab initio and double-hybrid density functional theory (DFT) methods. Structures of guanidinium...guanine complexes derived at the MP2/6-31+G** level of theory show that monomethylated, symmetrically dimethylated, and unsymmetrical dimethylated guanidiniums are all capable of forming guanidinium...guanine complexes. However, when cytosine is involved in a base pair to guanine, only the monomethylated and symmetrically dimethylated guanidinium groups are capable of forming hydrogen bond complexes with guanine. At the B2-PLYP/6-311++G** level of theory, we found that methylation of the guanidinium group stabilizes the formation of the guanidinium... guanine complex relative to the unmethylated guanidinium...guanine complex by approximately 2.5 kcal mol(-1). The biological implication of these findings are discussed.
精氨酸甲基化是一种蛋白质翻译后修饰，由称为精氨酸甲基转移酶（RMTs）的蛋白质催化。最近，精氨酸甲基化被认为是调节生物分子相互作用的一种重要修饰。RMTs主要作用于核蛋白，因此它们很可能有助于调节蛋白质……DNA相互作用。在本研究中，我们使用从头算和双杂化密度泛函理论（DFT）方法，探究了连续胍基甲基化对胍基……鸟嘌呤和胍基……鸟嘌呤……胞嘧啶复合物能量学的影响。在MP2/6 - 31 + G理论水平上推导得到的胍基……鸟嘌呤复合物结构表明，单甲基化、对称二甲基化和不对称二甲基化的胍都能够形成胍基……鸟嘌呤复合物。然而，当胞嘧啶与鸟嘌呤形成碱基对时，只有单甲基化和对称二甲基化的胍基团能够与鸟嘌呤形成氢键复合物。在B2 - PLYP/6 - 311++G理论水平上，我们发现相对于未甲基化的胍基……鸟嘌呤复合物，胍基的甲基化使胍基……鸟嘌呤复合物的形成稳定了约2.5千卡/摩尔（-1）。本文讨论了这些发现的生物学意义。
