蛋白酪氨酸磷酸酶 epsilon 的 D1 和 D2 结构域的高分辨率晶体结构，用于基于结构的药物设计。
High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design.
机构信息
Basic Science Program, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD 21702, USA.
Macromolecular Crystallography Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
出版信息
Acta Crystallogr D Struct Biol. 2018 Oct 1;74(Pt 10):1015-1026. doi: 10.1107/S2059798318011919. Epub 2018 Oct 2.
Here, new crystal structures are presented of the isolated membrane-proximal D1 and distal D2 domains of protein tyrosine phosphatase epsilon (PTPℇ), a protein tyrosine phosphatase that has been shown to play a positive role in the survival of human breast cancer cells. A triple mutant of the PTPℇ D2 domain (A455N/V457Y/E597D) was also constructed to reconstitute the residues of the PTPℇ D1 catalytic domain that are important for phosphatase activity, resulting in only a slight increase in the phosphatase activity compared with the native D2 protein. The structures reported here are of sufficient resolution for structure-based drug design, and a microarray-based assay for high-throughput screening to identify small-molecule inhibitors of the PTPℇ D1 domain is also described.
这里呈现了分离的蛋白酪氨酸磷酸酶 epsilon（PTPε）的膜近端 D1 结构域和远端 D2 结构域的新晶体结构，该蛋白酪氨酸磷酸酶已被证明在人类乳腺癌细胞的存活中发挥积极作用。还构建了 PTPε D2 结构域的三突变体（A455N/V457Y/E597D），以重新构建对磷酸酶活性重要的 PTPε D1 催化结构域的残基，导致与天然 D2 蛋白相比，磷酸酶活性仅略有增加。这里报道的结构具有足够的分辨率，可用于基于结构的药物设计，还描述了一种基于微阵列的高通量筛选检测方法，用于鉴定 PTPε D1 结构域的小分子抑制剂。
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