Methods for Identification of Substrates/Inhibitors of FCP/SCP Type Protein Ser/Thr Phosphatases
Methods for Identification of Substrates/Inhibitors of FCP/SCP Type Protein Ser/Thr Phosphatases
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DOI：
10.3390/pr8121598
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发表时间：
2020-12
期刊：
影响因子：
3.5
通讯作者：
Masataka Mizunuma;A. Kaneko;Shunta Imai;K. Furukawa;Y. Chuman
中科院分区：
文献类型：
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作者：
Masataka Mizunuma;A. Kaneko;Shunta Imai;K. Furukawa;Y. Chuman
蛋白磷酸化是最广泛的翻译后修饰类型，由蛋白激酶和磷酸酶适当控制。对于丝氨酸（Ser）和苏氨酸（Thr）残基的磷酸化，与丝氨酸/苏氨酸激酶相比，相对较少的蛋白质丝氨酸/苏氨酸磷酸酶控制着许多底物的特异性去磷酸化。近年来，蛋白质丝氨酸/苏氨酸磷酸酶被报道具有刚性底物识别并发挥多种生物学功能。因此，通过单个蛋白丝氨酸/苏氨酸磷酸酶鉴定靶蛋白对于阐明其自身的生物学功能至关重要。然而，迄今为止，关于鉴定丝氨酸/苏氨酸蛋白磷酸酶底物的方法的发展信息仍然很少。反过来，底物捕获突变体是搜索蛋白酪氨酸（Tyr）磷酸酶的单个底物的有力工具。本文综述了利用AlF4−/BeF3−的肽展示噬菌体文库鉴定丝氨酸/苏氨酸磷酸酶，特别是小c端结构域磷酸酶1 （Scp1）的新方法的发展，并讨论了推定抑制剂的鉴定。
Protein phosphorylation is the most widespread type of post-translational modification and is properly controlled by protein kinases and phosphatases. Regarding the phosphorylation of serine (Ser) and threonine (Thr) residues, relatively few protein Ser/Thr phosphatases control the specific dephosphorylation of numerous substrates, in contrast with Ser/Thr kinases. Recently, protein Ser/Thr phosphatases were reported to have rigid substrate recognition and exert various biological functions. Therefore, identification of targeted proteins by individual protein Ser/Thr phosphatases is crucial to clarify their own biological functions. However, to date, information on the development of methods for identification of the substrates of protein Ser/Thr phosphatases remains scarce. In turn, substrate-trapping mutants are powerful tools to search the individual substrates of protein tyrosine (Tyr) phosphatases. This review focuses on the development of novel methods for the identification of Ser/Thr phosphatases, especially small C-terminal domain phosphatase 1 (Scp1), using peptide-displayed phage library with AlF4−/BeF3−, and discusses the identification of putative inhibitors.