Generating orthogonal glycosyltransferase and nucleotide sugar pairs as next-generation glycobiology tools.
Generating orthogonal glycosyltransferase and nucleotide sugar pairs as next-generation glycobiology tools.
复制标题
产生正交糖基转移酶和核苷酸糖对作为下一代糖生物学工具。
DOI：
10.1016/j.cbpa.2020.09.001
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发表时间：
2021-03
影响因子：
7.8
通讯作者：
Schumann B
中科院分区：
文献类型：
--
作者：
Cioce A;Malaker SA;Schumann B
蛋白质糖基化从根本上影响生物过程。非模板化生物合成为聚糖引入了无与伦比的复杂性，需要工具来了解它们在生理学中的作用。定量生物学的时代是一个很好的机会来解开这些角色，特别是通过质谱糖蛋白组学。然而，高灵敏度带来了对工具特异性的严格要求。生物正交代谢标记试剂是研究细胞表面糖蛋白组的基础，但通常进入一系列不同的聚糖，因此特异性有限。在这里，我们讨论了代谢的“精确工具”，以研究特定亚型的糖组的一代。作为糖生物学的一项使能技术，一种被称为凸穴工程的化学生物学策略产生特异性地容纳生物正交单糖的突变糖基转移酶。我们回顾了突破性的发现，导致应用的战术在活细胞和影响的背景下，目前的发展，质谱糖蛋白组学。
Protein glycosylation fundamentally impacts biological processes. Nontemplated biosynthesis introduces unparalleled complexity into glycans that needs tools to understand their roles in physiology. The era of quantitative biology is a great opportunity to unravel these roles, especially by mass spectrometry glycoproteomics. However, with high sensitivity come stringent requirements on tool specificity. Bioorthogonal metabolic labeling reagents have been fundamental to studying the cell surface glycoproteome but typically enter a range of different glycans and are thus of limited specificity. Here, we discuss the generation of metabolic ‘precision tools’ to study particular subtypes of the glycome. A chemical biology tactic termed bump-and-hole engineering generates mutant glycosyltransferases that specifically accommodate bioorthogonal monosaccharides as an enabling technique of glycobiology. We review the groundbreaking discoveries that have led to applying the tactic in the living cell and the implications in the context of current developments in mass spectrometry glycoproteomics.