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

Lountos, George T.; Raran-Kurussi, Sreejith; Zhao, Bryan M.; Dyas, Beverly K.; Burke, Terrence R.; Ulrich, Robert G.; Waugh, David S.

doi:10.1107/S2059798318011919

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

Journal Article · Mon Oct 01 00:00:00 EDT 2018 · Acta Crystallographica. Section D. Structural Biology

DOI:https://doi.org/10.1107/S2059798318011919· OSTI ID:1506503

Lountos, George T.; Raran-Kurussi, Sreejith; Zhao, Bryan M.; Dyas, Beverly K.; Burke, Terrence R.; Ulrich, Robert G.; Waugh, David S.

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.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH)

OSTI ID:: 1506503

Journal Information:: Acta Crystallographica. Section D. Structural Biology, Vol. 74, Issue 10; ISSN 2059-7983

Publisher:: IUCr

Country of Publication:: United States

Language:: ENGLISH

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