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PDBsum entry 3cwe

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protein ligands metals links
Hydrolase PDB id
3cwe
Jmol
Contents
Protein chain
285 a.a. *
Ligands
825
Metals
_MG ×3
Waters ×318
* Residue conservation analysis
PDB id:
3cwe
Name: Hydrolase
Title: Ptp1b in complex with a phosphonic acid inhibitor
Structure: Tyrosine-protein phosphatase non-receptor type 1. Chain: a. Fragment: tyrosine-protein phosphatase domain. Synonym: protein-tyrosine phosphatase 1b, ptp-1b. Engineered: yes
Source: Homo sapiens. Human. Gene: ptpn1, ptp1b. Expressed in: escherichia coli.
Resolution:
1.60Å     R-factor:   0.177     R-free:   0.193
Authors: G.Scapin,Y.Han,B.P.Kennedy
Key ref: Y.Han et al. (2008). Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro)methyl]phosphonic acid, a potent and orally active small molecule PTP1B inhibitor. Bioorg Med Chem Lett, 18, 3200-3205. PubMed id: 18477508
Date:
21-Apr-08     Release date:   10-Jun-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 Enzyme reactions 
   Enzyme class: E.C.3.1.3.48  - 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  

 

 
    reference    
 
 
Bioorg Med Chem Lett 18:3200-3205 (2008)
PubMed id: 18477508  
 
 
Discovery of [(3-bromo-7-cyano-2-naphthyl)(difluoro)methyl]phosphonic acid, a potent and orally active small molecule PTP1B inhibitor.
Y.Han, M.Belley, C.I.Bayly, J.Colucci, C.Dufresne, A.Giroux, C.K.Lau, Y.Leblanc, D.McKay, M.Therien, M.C.Wilson, K.Skorey, C.C.Chan, G.Scapin, B.P.Kennedy.
 
  ABSTRACT  
 
A series of quinoline/naphthalene-difluoromethylphosphonates were prepared and were found to be potent PTP1B inhibitors. Most of these compounds bearing polar functionalities or large lipophilic residues did not show appreciable oral bioavailability in rodents while small and less polar analogs displayed moderate to good oral bioavailability. The title compound was found to have the best overall potency and pharmacokinetic profile and was found to be efficacious in animal models of diabetes and cancer.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21420867 V.V.Vintonyak, H.Waldmann, and D.Rauh (2011).
Using small molecules to target protein phosphatases.
  Bioorg Med Chem, 19, 2145-2155.  
21135139 E.Nievergall, P.W.Janes, C.Stegmayer, M.E.Vail, F.G.Haj, S.W.Teng, B.G.Neel, P.I.Bastiaens, and M.Lackmann (2010).
PTP1B regulates Eph receptor function and trafficking.
  J Cell Biol, 191, 1189-1203.  
20644889 K.A.Rawls, C.Grundner, and J.A.Ellman (2010).
Design and synthesis of nonpeptidic, small molecule inhibitors for the Mycobacterium tuberculosis protein tyrosine phosphatase PtpB.
  Org Biomol Chem, 8, 4066-4070.  
19889539 K.A.Rawls, P.T.Lang, J.Takeuchi, S.Imamura, T.D.Baguley, C.Grundner, T.Alber, and J.A.Ellman (2009).
Fragment-based discovery of selective inhibitors of the Mycobacterium tuberculosis protein tyrosine phosphatase PtpA.
  Bioorg Med Chem Lett, 19, 6851-6854.  
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.