PDBsum entry 4rhg

Hydrolase/protein binding

PDB id: 4rhg

Contents

Protein chain

282 a.a.

Ligands

PHE-SER-ALA-PTR-PRO-SER-GLU

Waters ×213

PDB id:

4rhg

Name:

Hydrolase/protein binding

Title:

Crystal structure of ptpn3 (ptph1) d811e, c842s mutant in complex with eps15 ptyr849 peptide

Structure:

Tyrosine-protein phosphatase non-receptor type 3. Chain: a. Fragment: catalytic domain (unp residues 628-909). Synonym: protein-tyrosine phosphatase h1, ptp-h1. Engineered: yes. Mutation: yes. Epidermal growth factor receptor substrate 15. Chain: b. Fragment: ptyr849 peptide (unp residues 846-854).

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ptph1, ptpn3. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic construct

Resolution:

1.58Å R-factor: 0.185 R-free: 0.209

Authors:

K.-E.Chen,T.C.Meng,A.H.-J.Wang

Key ref:

K.E.Chen et al. (2015). Substrate specificity and plasticity of FERM-containing protein tyrosine phosphatases. Structure, 23, 653-664. PubMed id: 25728925 DOI: 10.1016/j.str.2015.01.017

Date:

02-Oct-14 Release date: 11-Mar-15

Protein chain

P26045  (PTN3_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 3 from Homo sapiens

Seq: 913 a.a.

Struc: 282 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.3.48 - protein-tyrosine-phosphatase.
• Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Key reference

DOI no: 10.1016/j.str.2015.01.017

Structure 23:653-664 (2015)

PubMed id: 25728925

Substrate specificity and plasticity of FERM-containing protein tyrosine phosphatases.

K.E.Chen, M.Y.Li, C.C.Chou, M.R.Ho, G.C.Chen, T.C.Meng, A.H.Wang.

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.