4RH9

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

4RH9 の概要

• エントリーDOI: 10.2210/pdb4rh9/pdb
• 関連するPDBエントリー: 2B49 4QUM 4RH5 4RHG 4RI4 4RI5
• 分子名称: Tyrosine-protein phosphatase non-receptor type 3, Epidermal growth factor receptor substrate 15 (3 entities in total)
• 機能のキーワード: alpha beta, hydrolase-protein binding complex, hydrolase/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35946.55

構造登録者

Chen, K.-E.,Meng, T.C.,Wang, A.H.-J. (登録日: 2014-10-01, 公開日: 2015-03-11, 最終更新日: 2023-12-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.598 Å)