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Title: 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 (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.

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1506503
Resource Type:
Journal Article
Journal Name:
Acta Crystallographica. Section D. Structural Biology
Additional Journal Information:
Journal Volume: 74; Journal Issue: 10; Journal ID: ISSN 2059-7983
Publisher:
IUCr
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Lountos, George T., Raran-Kurussi, Sreejith, Zhao, Bryan M., Dyas, Beverly K., Burke, Terrence R., Ulrich, Robert G., and Waugh, David S. High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design. United States: N. p., 2018. Web. doi:10.1107/S2059798318011919.
Lountos, George T., Raran-Kurussi, Sreejith, Zhao, Bryan M., Dyas, Beverly K., Burke, Terrence R., Ulrich, Robert G., & Waugh, David S. High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design. United States. doi:10.1107/S2059798318011919.
Lountos, George T., Raran-Kurussi, Sreejith, Zhao, Bryan M., Dyas, Beverly K., Burke, Terrence R., Ulrich, Robert G., and Waugh, David S. Mon . "High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design". United States. doi:10.1107/S2059798318011919.
@article{osti_1506503,
title = {High-resolution crystal structures of the D1 and D2 domains of protein tyrosine phosphatase epsilon for structure-based drug design},
author = {Lountos, George T. and Raran-Kurussi, Sreejith and Zhao, Bryan M. and Dyas, Beverly K. and Burke, Terrence R. and Ulrich, Robert G. and Waugh, David S.},
abstractNote = {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.},
doi = {10.1107/S2059798318011919},
journal = {Acta Crystallographica. Section D. Structural Biology},
issn = {2059-7983},
number = 10,
volume = 74,
place = {United States},
year = {2018},
month = {10}
}

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