PDBsum entry 5j8r

Hydrolase

PDB id: 5j8r

Contents

Protein chains

296 a.a.

Waters ×377

PDB id:

5j8r

Name:

Hydrolase

Title:

Crystal structure of the catalytic domain of human protein tyrosine phosphatase non-receptor type 12 - k61r mutant

Structure:

Tyrosine-protein phosphatase non-receptor type 12. Chain: a, b, c, d. Fragment: unp residues 1-305. Synonym: ptp-pest,protein-tyrosine phosphatase g1,ptpg1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn12. Expressed in: escherichia coli. Expression_system_taxid: 511693.

Resolution:

2.04Å R-factor: 0.241 R-free: 0.275

Authors:

H.Li,F.Yang,Y.F.Xu,W.J.Wang,P.Xiao,X.Yu,J.P.Sun

Key ref:

H.Li et al. (2016). Crystal Structure and Substrate Specificity of PTPN12. Cell Rep, 15, 1345-1358. PubMed id: 27134172 DOI: 10.1016/j.celrep.2016.04.016

Date:

08-Apr-16 Release date: 27-Apr-16

Protein chains

Q05209  (PTN12_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 12 from Homo sapiens

Seq: 780 a.a.

Struc: 296 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

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.celrep.2016.04.016

Cell Rep 15:1345-1358 (2016)

PubMed id: 27134172

Crystal Structure and Substrate Specificity of PTPN12.

H.Li, F.Yang, C.Liu, P.Xiao, Y.Xu, Z.Liang, C.Liu, H.Wang, W.Wang, W.Zheng, W.Zhang, X.Ma, D.He, X.Song, F.Cui, Z.Xu, F.Yi, J.P.Sun, X.Yu.

ABSTRACT

PTPN12 is an important tumor suppressor that plays critical roles in various physiological processes. However, the molecular basis underlying the substrate specificity of PTPN12 remains uncertain. Here, enzymological and crystallographic studies have enabled us to identify two distinct structural features that are crucial determinants of PTPN12 substrate specificity: the pY+1 site binding pocket and specific basic charged residues along its surface loops. Key structurally plastic regions and specific residues in PTPN12 enabled recognition of different HER2 phosphorylation sites and regulated specific PTPN12 functions. In addition, the structure of PTPN12 revealed a CDK2 phosphorylation site in a specific PTPN12 loop. Taken together, our results not only provide the working mechanisms of PTPN12 for desphosphorylation of its substrates but will also help in designing specific inhibitors of PTPN12.