PDBsum entry 4qun

Hydrolase

PDB id: 4qun

Contents

Protein chains

283 a.a.

Ligands

PO4 ×2

GOL

Waters ×338

PDB id:

4qun

Name:

Hydrolase

Title:

Crystal structure of the ptpn3 (ptph1) catalytic domain c842s mutant

Structure:

Tyrosine-protein phosphatase non-receptor type 3. Chain: a, b. Fragment: catalytic domain (unp residues 628-909). Synonym: protein-tyrosine phosphatase h1, ptp-h1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ptph1, ptpn3. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.86Å R-factor: 0.179 R-free: 0.206

Authors:

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

Key ref:

K.E.Chen et al. (2014). Reciprocal allosteric regulation of p38γ and PTPN3 involves a PDZ domain-modulated complex formation. Sci Signal, 7, ra98. PubMed id: 25314968 DOI: 10.1126/scisignal.2005722

Date:

11-Jul-14 Release date: 10-Dec-14

Protein chains

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

Seq: 913 a.a.

Struc: 283 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

O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly)

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

Key reference

DOI no: 10.1126/scisignal.2005722

Sci Signal 7:ra98 (2014)

PubMed id: 25314968

Reciprocal allosteric regulation of p38γ and PTPN3 involves a PDZ domain-modulated complex formation.

K.E.Chen, S.Y.Lin, M.J.Wu, M.R.Ho, A.Santhanam, C.C.Chou, T.C.Meng, A.H.Wang.

ABSTRACT

The mitogen-activated protein kinase p38γ (also known as MAPK12) and its specific phosphatase PTPN3 (also known as PTPH1) cooperate to promote Ras-induced oncogenesis. We determined the architecture of the PTPN3-p38γ complex by a hybrid method combining x-ray crystallography, small-angle x-ray scattering, and chemical cross-linking coupled to mass spectrometry. A unique feature of the glutamic acid-containing loop (E-loop) of the phosphatase domain defined the substrate specificity of PTPN3 toward fully activated p38γ. The solution structure revealed the formation of an active-state complex between p38γ and the phosphatase domain of PTPN3. The PDZ domain of PTPN3 stabilized the active-state complex through an interaction with the PDZ-binding motif of p38γ. This interaction alleviated autoinhibition of PTPN3, enabling efficient tyrosine dephosphorylation of p38γ. Our findings may enable structure-based drug design targeting the PTPN3-p38γ interaction as an anticancer therapeutic.