磷酸化组氨酸研究进展

The Progress in Phosphohistidine Research

蛋白质磷酸化是生物体内一种广泛存在的蛋白质翻译后修饰形式,这种氨基酸与磷酸基团共价连接的修饰模式对蛋白质结构和功能起到了重要调节作用.目前天然蛋白质中发现的可磷酸化位点主要有9种氨基酸残基,其中包括以磷酰胺连接的磷酸化组氨酸.虽然该磷酸化形式在原核生物与真核生物中都起到了重要的调节作用,但对于其生物学功能的研究长期存在技术困难.由于磷酸化组氨酸本身不同于其他磷酸化氨基酸的化学性质,如存在异构体、化学不稳定等,其在传统的研究方法中容易发生水解去磷酸化.随着现代生物化学与分子生物学技术的不断进步,人们针对含有磷酸化组氨酸的蛋白质构建了新的制备、分离与表征策略,本领域也因此开始迅速发展.本文从磷酸化组氨酸的化学结构入手,分析其两种异构体的主要理化性质与化学反应特性,并概述了基于此发展的新型化学生物学研究手段以及对于磷酸化组氨酸生物功能的研究进展.

Protein phosphorylation is a wide existing protein post-translational modification in living organisms. This covalently linking mode between a certain amino acid and a phosphate group plays a sophisticated role in the regulation of protein stuctures and functions. Nowadays, nine amino acid residues have been found to have the capacity of phosphorylation, including histidine via a phosphamide bond. Although histidine phosphorylation has a significant regulatory function in both prokaryotic and eukaryotic cells, there has been seldom unimpeachable solution for the biologic research for a long time. Because of the diverse chemical properties of phosphohistidine per se from other phosphorylated amino acids, such as isomerism, chemical lability etc, it hydrolyzes easily during traditional handling methods. Due to the current progress in biochemistry and molecular biology, investigators have established innovative preparation, isolation and characterization strategies for phosphohistidine ad hoc. Therefore, the field begins to rapidly develop. Based on their chemical structures, this article analyzes the main physical and chemical properties as well as their reactivity of two phosphohistidine isomers, followed by the noval chemical biology tools and the main biological progresses.