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High‐resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure‐based drug design
Author(s) -
Lountos George T.,
Raran-Kurussi Sreejith,
Zhao Bryan M.,
Dyas Beverly K.,
Burke Terrence R.,
Ulrich Robert G.,
Waugh David S.
Publication year - 2018
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798318011919
Subject(s) - protein tyrosine phosphatase , phosphatase , mutant , tyrosine , chemistry , enzyme , biochemistry , biology , gene
Here, new crystal structures are presented of the isolated membrane‐proximal D1 and distal D2 domains of protein tyrosine phosphatase epsilon (PTPϵ), 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 PTPϵ D2 domain (A455N/V457Y/E597D) was also constructed to reconstitute the residues of the PTPϵ 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 PTPϵ D1 domain is also described.