4RH9

Crystal structure of PTPN3 (PTPH1) H812F, M883G mutant in complex with Eps15 pTyr849 peptide

Summary for 4RH9

• Entry DOI: 10.2210/pdb4rh9/pdb
• Related: 2B49 4QUM 4RH5 4RHG 4RI4 4RI5
• Descriptor: Tyrosine-protein phosphatase non-receptor type 3, Epidermal growth factor receptor substrate 15 (3 entities in total)
• Functional Keywords: alpha beta, hydrolase-protein binding complex, hydrolase/protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 35946.55

Authors

Chen, K.-E.,Meng, T.C.,Wang, A.H.-J. (deposition date: 2014-10-01, release date: 2015-03-11, Last modification date: 2023-12-06)

Primary citation

Chen, K.E.,Li, M.Y.,Chou, C.C.,Ho, M.R.,Chen, G.C.,Meng, T.C.,Wang, A.H.
Substrate specificity and plasticity of FERM-containing protein tyrosine phosphatases.
Structure, 23:653-664, 2015

PubMed Abstract: Epidermal growth factor receptor (EGFR) pathway substrate 15 (Eps15) is a newly identified substrate for protein tyrosine phosphatase N3 (PTPN3), which belongs to the FERM-containing PTP subfamily comprising five members including PTPN3, N4, N13, N14, and N21. We solved the crystal structures of the PTPN3-Eps15 phosphopeptide complex and found that His812 of PTPN3 and Pro850 of Eps15 are responsible for the specific interaction between them. We defined the critical role of the additional residue Tyr676 of PTPN3, which is replaced by Ile939 in PTPN14, in recognition of tyrosine phosphorylated Eps15. The WPD loop necessary for catalysis is present in all members but not PTPN21. We identified that Glu instead of Asp in the WPE loop contributes to the catalytic incapability of PTPN21 due to an extended distance beyond protonation targeting a phosphotyrosine substrate. Together with in vivo validations, our results provide novel insights into the substrate specificity and plasticity of FERM-containing PTPs.

PubMed: 25728925
DOI: 10.1016/j.str.2015.01.017

Experimental method

X-RAY DIFFRACTION (1.598 Å)