Posttranslational modifications can alter protein structures, functions and locations, and are important cellular regulatory and signalling mechanisms. Spectroscopic techniques such as nuclear magnetic resonance, infrared and Raman spectroscopy, as well as small-angle scattering, can provide insights into the structural and dynamic effects of protein posttranslational modifications and their impact on interactions with binding partners. However, heterogeneity of modified proteins from natural sources and spectral complexity often hinder analyses, especially for large proteins and macromolecular assemblies. Selective labelling of proteins with stable isotopes can greatly simplify spectra, as one can focus on labelled residues or segments of interest. Employing chemical biology tools for modifying and isotopically labelling proteins with atomic precision provides access to unique protein samples for structural biology and spectroscopy. Here, we review site-specific and segmental isotope labelling methods that are employed in combination with chemical and enzymatic tools to access posttranslationally modified proteins. We discuss illustrative examples in which these methods have been used to facilitate spectroscopic studies of posttranslationally modified proteins, providing new insights into biology.

中文翻译：

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用于翻译后修饰蛋白质结构分析的片段和位点特异性同位素标记策略

翻译后修饰可以改变蛋白质结构、功能和位置，并且是重要的细胞调节和信号传导机制。核磁共振、红外和拉曼光谱以及小角度散射等光谱技术可以深入了解蛋白质翻译后修饰的结构和动态效应及其对与结合伙伴相互作用的影响。然而，来自天然来源的修饰蛋白质的异质性和光谱复杂性通常会阻碍分析，尤其是对于大蛋白质和大分子组件。用稳定同位素选择性标记蛋白质可以大大简化光谱，因为人们可以专注于标记的残基或感兴趣的片段。采用化学生物学工具以原子精度修饰和同位素标记蛋白质，为结构生物学和光谱学提供了独特的蛋白质样品。在这里，我们回顾了与化学和酶促工具结合使用以访问翻译后修饰的蛋白质的位点特定和分段同位素标记方法。我们讨论了这些方法用于促进翻译后修饰蛋白质的光谱研究的说明性例子，为生物学提供了新的见解。