PDBsum entry 4ge5

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Hydrolase/hydrolase inhibitor PDB id
Protein chains
298 a.a.
Waters ×356
PDB id:
Name: Hydrolase/hydrolase inhibitor
Title: Crystal structure of human protein tyrosine phosphatase ptpn complex with compound 5
Structure: Tyrosine-protein phosphatase non-receptor type 9. Chain: a, b. Fragment: tyrosine-protein phosphatase domain (unp residues synonym: protein-tyrosine phosphatase meg2, ptpase meg2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn9. Expressed in: escherichia coli. Expression_system_taxid: 469008.
2.00Å     R-factor:   0.187     R-free:   0.223
Authors: Z.-Y.Zhang,S.Liu,S.Zhang
Key ref: S.Zhang et al. (2012). A highly selective and potent PTP-MEG2 inhibitor with therapeutic potential for type 2 diabetes. J Am Chem Soc, 134, 18116-18124. PubMed id: 23075115 DOI: 10.1021/ja308212y
01-Aug-12     Release date:   31-Oct-12    
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Protein chains
Pfam   ArchSchema ?
P43378  (PTN9_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 9
593 a.a.
298 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.  - Protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Protein tyrosine phosphate + H2O = protein tyrosine + phosphate
Protein tyrosine phosphate
+ H(2)O
= protein tyrosine
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     dephosphorylation   2 terms 
  Biochemical function     phosphatase activity     2 terms  


DOI no: 10.1021/ja308212y J Am Chem Soc 134:18116-18124 (2012)
PubMed id: 23075115  
A highly selective and potent PTP-MEG2 inhibitor with therapeutic potential for type 2 diabetes.
S.Zhang, S.Liu, R.Tao, D.Wei, L.Chen, W.Shen, Z.H.Yu, L.Wang, D.R.Jones, X.C.Dong, Z.Y.Zhang.
Protein tyrosine phosphatases (PTPs) constitute a large family of signaling enzymes that control the cellular levels of protein tyrosine phosphorylation. A detailed understanding of PTP functions in normal physiology and in pathogenic conditions has been hampered by the absence of PTP-specific, cell-permeable small-molecule agents. We present a stepwise focused library approach that transforms a weak and general non-hydrolyzable pTyr mimetic (F(2)Pmp, phosphonodifluoromethyl phenylalanine) into a highly potent and selective inhibitor of PTP-MEG2, an antagonist of hepatic insulin signaling. The crystal structures of the PTP-MEG2-inhibitor complexes provide direct evidence that potent and selective PTP inhibitors can be obtained by introducing molecular diversity into the F(2)Pmp scaffold to engage both the active site and unique nearby peripheral binding pockets. Importantly, the PTP-MEG2 inhibitor possesses highly efficacious cellular activity and is capable of augmenting insulin signaling and improving insulin sensitivity and glucose homeostasis in diet-induced obese mice. The results indicate that F(2)Pmp can be converted into highly potent and selective PTP inhibitory agents with excellent in vivo efficacy. Given the general nature of the approach, this strategy should be applicable to other members of the PTP superfamily.