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Hydrolase PDB id
Protein chain
299 a.a. *
Waters ×143
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Ptp1b complexed with isoxazole carboxylic acid
Structure: Protein-tyrosine phosphatase, non-receptor type 1. Chain: a. Fragment: ptp1b catalytic domain. Synonym: protein-tyrosine phosphatase 1b, ptp-1b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn1, ptp1b. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.50Å     R-factor:   0.211     R-free:   0.219
Authors: H.Zhao,G.Liu,Z.Xin,M.Serby,Z.Pei,B.G.Szczepankiewicz, P.J.Hajduk,C.Abad-Zapatero,C.W.Hutchins,T.H.Lubben, S.J.Ballaron,D.L.Hassach,W.Kaszubska,C.M.Rondinone, J.M.Trevillyan,M.R.Jirousek
Key ref: H.Zhao et al. (2004). Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors. Bioorg Med Chem Lett, 14, 5543-5546. PubMed id: 15482920 DOI: 10.1016/j.bmcl.2004.08.063
31-Aug-04     Release date:   19-Oct-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1
435 a.a.
299 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 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: 10.1016/j.bmcl.2004.08.063 Bioorg Med Chem Lett 14:5543-5546 (2004)
PubMed id: 15482920  
Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors.
H.Zhao, G.Liu, Z.Xin, M.D.Serby, Z.Pei, B.G.Szczepankiewicz, P.J.Hajduk, C.Abad-Zapatero, C.W.Hutchins, T.H.Lubben, S.J.Ballaron, D.L.Haasch, W.Kaszubska, C.M.Rondinone, J.M.Trevillyan, M.R.Jirousek.
Guided by X-ray crystallography, we have extended the structure-activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor (1) and more potent and equally selective (>20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified. Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20350805 F.Liu, R.M.Hakami, B.Dyas, M.Bahta, G.T.Lountos, D.S.Waugh, R.G.Ulrich, and T.R.Burke (2010).
A rapid oxime linker-based library approach to identification of bivalent inhibitors of the Yersinia pestis protein-tyrosine phosphatase, YopH.
  Bioorg Med Chem Lett, 20, 2813-2816.  
19240079 N.J.Beresford, D.Mulhearn, B.Szczepankiewicz, G.Liu, M.E.Johnson, A.Fordham-Skelton, C.Abad-Zapatero, J.S.Cavet, and L.Tabernero (2009).
Inhibition of MptpB phosphatase from Mycobacterium tuberculosis impairs mycobacterial survival in macrophages.
  J Antimicrob Chemother, 63, 928-936.  
19288492 R.Maccari, R.Ottanà, R.Ciurleo, P.Paoli, G.Manao, G.Camici, C.Laggner, and T.Langer (2009).
Structure-based optimization of benzoic acids as inhibitors of protein tyrosine phosphatase 1B and low molecular weight protein tyrosine phosphatase.
  ChemMedChem, 4, 957-962.  
17275735 H.Zhao (2007).
Scaffold selection and scaffold hopping in lead generation: a medicinal chemistry perspective.
  Drug Discov Today, 12, 149-155.  
17543532 R.Maccari, P.Paoli, R.Ottanà, M.Jacomelli, R.Ciurleo, G.Manao, T.Steindl, T.Langer, M.G.Vigorita, and G.Camici (2007).
5-Arylidene-2,4-thiazolidinediones as inhibitors of protein tyrosine phosphatases.
  Bioorg Med Chem, 15, 5137-5149.  
17039461 S.Lee, and Q.Wang (2007).
Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B.
  Med Res Rev, 27, 553-573.  
16364216 G.X.Liu, J.Z.Tan, C.Y.Niu, J.H.Shen, X.M.Luo, X.Shen, K.X.Chen, and H.L.Jiang (2006).
Molecular dynamics simulations of interaction between protein-tyrosine phosphatase 1B and a bidentate inhibitor.
  Acta Pharmacol Sin, 27, 100-110.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time.