PDBsum entry 3jrl

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protein ligands links
Hydrolase PDB id
Protein chain
255 a.a. *
Waters ×123
* Residue conservation analysis
Superseded by: 3o5x
PDB id:
Name: Hydrolase
Title: Crystal structure of the oncogenic tyrosine phosphatase shp2 with a salicylic acid-based small molecule inhibitor
Structure: Oncogenic tyrosine phosphatase shp2. Chain: a. Fragment: unp residues 262-528, catalytic domain. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn11. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.00Å     R-factor:   0.195     R-free:   0.251
Authors: X.Zhang,Y.T.He,S.Liu,Z.H.Yu,L.Wu,Z.Y.Zhang
Key ref: X.Zhang et al. (2010). Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). J Med Chem, 53, 2482-2493. PubMed id: 20170098
08-Sep-09     Release date:   02-Mar-10    
Go to PROCHECK summary

Protein chain
A8K1D9  (A8K1D9_HUMAN) - 
Key:    Secondary structure


J Med Chem 53:2482-2493 (2010)
PubMed id: 20170098  
Salicylic acid based small molecule inhibitor for the oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2).
X.Zhang, Y.He, S.Liu, Z.Yu, Z.X.Jiang, Z.Yang, Y.Dong, S.C.Nabinger, L.Wu, A.M.Gunawan, L.Wang, R.J.Chan, Z.Y.Zhang.
The Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) plays a pivotal role in growth factor and cytokine signaling. Gain-of-function SHP2 mutations are associated with Noonan syndrome, various kinds of leukemias, and solid tumors. Thus, there is considerable interest in SHP2 as a potential target for anticancer and antileukemia therapy. We report a salicylic acid based combinatorial library approach aimed at binding both active site and unique nearby subpockets for enhanced affinity and selectivity. Screening of the library led to the identification of a SHP2 inhibitor II-B08 (compound 9) with highly efficacious cellular activity. Compound 9 blocks growth factor stimulated ERK1/2 activation and hematopoietic progenitor proliferation, providing supporting evidence that chemical inhibition of SHP2 may be therapeutically useful for anticancer and antileukemia treatment. X-ray crystallographic analysis of the structure of SHP2 in complex with 9 reveals molecular determinants that can be exploited for the acquisition of more potent and selective SHP2 inhibitors.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21290544 J.Hu, J.Wu, C.Li, L.Zhu, W.Y.Zhang, G.Kong, Z.Lu, and C.J.Yang (2011).
A G-quadruplex aptamer inhibits the phosphatase activity of oncogenic protein Shp2 in vitro.
  Chembiochem, 12, 424-430.  
21276943 S.Liu, Z.Yu, X.Yu, S.X.Huang, Y.Luo, L.Wu, W.Shen, Z.Yang, L.Wang, A.M.Gunawan, R.J.Chan, B.Shen, and Z.Y.Zhang (2011).
SHP2 is a target of the immunosuppressant tautomycetin.
  Chem Biol, 18, 101-110.  
21420867 V.V.Vintonyak, H.Waldmann, and D.Rauh (2011).
Using small molecules to target protein phosphatases.
  Bioorg Med Chem, 19, 2145-2155.  
20957718 R.He, Z.Yu, Y.He, L.F.Zeng, J.Xu, L.Wu, A.M.Gunawan, L.Wang, Z.X.Jiang, and Z.Y.Zhang (2010).
Double click reaction for the acquisition of a highly potent and selective mPTPB inhibitor.
  ChemMedChem, 5, 2051-2056.  
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