School of Biotechnology, International University-Vietnam National University in HCMC, Ho Chi Minh City, 720351, Vietnam.
Proteomics. 2019 May;19(10):e1700471. doi: 10.1002/pmic.201700471. Epub 2018 Dec 27.
Protein post-translational modifications (PTMs) are important modulators of virtually all cellular processes, and frequently correlate with not only the rate but also severity of diseases. There has been considerable interest to map all possible PTM sites to be used as drug targets. Current approaches for PTM analysis suffer from a number of challenges; one of which is the lack of a PTM specific cleaving reagent. A central technology for global quantitative PTM analysis, mass spectrometry (MS) based proteomics, is biased toward trypsin due to its high activity and specificity. This bias becomes a problem when a PTM is located at or near tryptic cleavage sites, in which case the PTM might block recognition by trypsin, resulting in missed cleavage and sequence coverage gaps. Reviewed here are recent advances in engineering new proteases for PTM analyses, and how these new proteases are beginning to address current challenges in the field.
蛋白质翻译后修饰（PTMs）是几乎所有细胞过程的重要调节剂，并且经常与疾病的速度和严重程度都有关。人们一直有相当大的兴趣来绘制所有可能的 PTM 位点，将其用作药物靶点。目前的 PTM 分析方法存在许多挑战；其中之一是缺乏 PTM 特异性切割试剂。基于质谱（MS）的蛋白质组学是一种用于全局定量 PTM 分析的核心技术，由于其高活性和特异性，它偏向于胰蛋白酶。当 PTM 位于或靠近胰蛋白酶切割位点时，这种偏见就会成为一个问题，在这种情况下，PTM 可能会阻止胰蛋白酶的识别，导致切割缺失和序列覆盖缺口。本文综述了用于 PTM 分析的新型蛋白酶的最新进展，以及这些新型蛋白酶如何开始解决该领域当前的挑战。
