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High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design.

ABSTRACT: Here, new crystal structures are presented of the isolated membrane-proximal D1 and distal D2 domains of protein tyrosine phosphatase epsilon (PTP?), 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 PTP? D2 domain (A455N/V457Y/E597D) was also constructed to reconstitute the residues of the PTP? 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 PTP? D1 domain is also described.

SUBMITTER: Lountos GT

PROVIDER: S-EPMC6173050 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design.

Lountos George T GT Raran-Kurussi Sreejith S Zhao Bryan M BM Dyas Beverly K BK Burke Terrence R TR Ulrich Robert G RG Waugh David S DS

Acta crystallographica. Section D, Structural biology 20181002 Pt 10

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 p ...[more]

PMID: 30289412

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