Mavri J, Vogel H J
BIOSON Research Institute, Department of Biophysical Chemistry, University of Groningen, The Netherlands.
Proteins. 1996 Apr;24(4):495-501. doi: 10.1002/(SICI)1097-0134(199604)24:4<495::AID-PROT8>3.0.CO;2-D.
Protein phosphorylation is one of the major signal transduction mechanisms for controlling and regulating intracellular processes. Phosphorylation of specific hydroxylated amino acid side chains (Ser, Thr, Tyr) by protein kinases can activate numerous enzymes; this effect can be reversed by the action of protein phosphatases. Here we report ab initio (HF/6-31G and Becke3LYP/6-31G) and semiempirical (PM3) molecular orbital calculations pertinent to the ion pair formation of the phosphorylated amino acids with the basic side chains of Lys and Arg. Methyl-, ethyl-, and phenylphosphate, as well as methylamine and methylguanidinium were used as model compounds for the phosphorylated and basic amino acids, respectively. Phosphorylated amino acids were calculated as mono- and divalent anions. Our results indicate that the PSer/PThr ion pair interaction energies are stronger than those with PTyr. Moreover, the interaction energies with the amino group of Lys are generally more favorable than with the guanidinium group of Arg. The Lys amino groups form stable bifurcated hydrogen bonded structures; while the Arg guanidinium group can form a bidentate hydrogen bonded structure. Reasonable values for the interaction free energies in aqueous solution were obtained for some complexes by the inclusion of a solvent reaction field in the computation (PM3-SM3).
蛋白质磷酸化是控制和调节细胞内过程的主要信号转导机制之一。蛋白激酶对特定羟基化氨基酸侧链（丝氨酸、苏氨酸、酪氨酸）的磷酸化可激活多种酶；这种效应可被蛋白磷酸酶的作用逆转。本文报道了与磷酸化氨基酸与赖氨酸和精氨酸碱性侧链形成离子对相关的从头算（HF/6-31G和Becke3LYP/6-31G）和半经验（PM3）分子轨道计算。分别使用甲基磷酸酯、乙基磷酸酯、苯基磷酸酯以及甲胺和甲基胍作为磷酸化氨基酸和碱性氨基酸的模型化合物。磷酸化氨基酸被计算为单价和二价阴离子。我们的结果表明，磷酸化丝氨酸/磷酸化苏氨酸离子对的相互作用能比与磷酸化酪氨酸的相互作用能更强。此外，与赖氨酸氨基的相互作用能通常比与精氨酸胍基的相互作用能更有利。赖氨酸氨基形成稳定的分叉氢键结构；而精氨酸胍基可形成双齿氢键结构。通过在计算中包含溶剂反应场（PM3-SM3），获得了一些配合物在水溶液中相互作用自由能的合理值。
