Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
Bioconjug Chem. 2012 Dec 19;23(12):2386-91. doi: 10.1021/bc300404s. Epub 2012 Nov 13.
Kinase-catalyzed protein phosphorylation is an important biochemical process involved in cellular functions. We recently discovered that kinases promiscuously accept γ-modified ATP analogues as cosubstrates and used several ATP analogues as tools for studying protein phosphorylation. Herein, we explore the structural requirements of γ-modified ATP analogues for kinase compatibility. To understand the influence of linker length and composition, a series of ATP analogues was synthesized, and the efficiency of kinase-catalyzed labeling was determined by quantitative mass spectrometry. This study on factors influencing kinase cosubstrate promiscuity will enable design of ATP analogues for a variety of kinase-catalyzed labeling reactions.
激酶催化的蛋白磷酸化是参与细胞功能的一个重要生化过程。我们最近发现，激酶可以不加区分地接受γ修饰的 ATP 类似物作为共底物，并使用几种 ATP 类似物作为研究蛋白磷酸化的工具。在此，我们探讨了γ修饰的 ATP 类似物与激酶兼容性的结构要求。为了了解连接基团长度和组成的影响，合成了一系列 ATP 类似物，并通过定量质谱法确定了激酶催化标记的效率。这项关于影响激酶共底物混杂性因素的研究将使设计用于各种激酶催化标记反应的 ATP 类似物成为可能。
