PDBsum entry 2qbs

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Hydrolase PDB id
Protein chain
297 a.a. *
Waters ×223
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of ptp1b-inhibitor complex
Structure: Tyrosine-protein phosphatase non-receptor type 1. Chain: a. Fragment: tyrosine-protein phosphatase domain, 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
2.10Å     R-factor:   0.193     R-free:   0.229
Authors: W.Xu
Key ref: D.P.Wilson et al. (2007). Structure-based optimization of protein tyrosine phosphatase 1B inhibitors: from the active site to the second phosphotyrosine binding site. J Med Chem, 50, 4681-4698. PubMed id: 17705360 DOI: 10.1021/jm0702478
18-Jun-07     Release date:   18-Mar-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1
435 a.a.
297 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: 10.1021/jm0702478 J Med Chem 50:4681-4698 (2007)
PubMed id: 17705360  
Structure-based optimization of protein tyrosine phosphatase 1B inhibitors: from the active site to the second phosphotyrosine binding site.
D.P.Wilson, Z.K.Wan, W.X.Xu, S.J.Kirincich, B.C.Follows, D.Joseph-McCarthy, K.Foreman, A.Moretto, J.Wu, M.Zhu, E.Binnun, Y.L.Zhang, M.Tam, D.V.Erbe, J.Tobin, X.Xu, L.Leung, A.Shilling, S.Y.Tam, T.S.Mansour, J.Lee.
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin receptor pathways and thus an attractive therapeutic target for diabetes and obesity. Starting with a high micromolar lead compound, structure-based optimization of novel PTP1B inhibitors by extension of the molecule from the enzyme active site into the second phosphotyrosine binding site is described. Medicinal chemistry, guided by X-ray complex structure and molecular modeling, has yielded low nanomolar PTP1B inhibitors in an efficient manner. Compounds from this chemical series were found to be actively transported into hepatocytes. This active uptake into target tissues could be one of the possible avenues to overcome the poor membrane permeability of PTP1B inhibitors.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20815942 P.Stegmaier, M.Krull, N.Voss, A.E.Kel, and E.Wingender (2010).
Molecular mechanistic associations of human diseases.
  BMC Syst Biol, 4, 124.  
20686525 Z.Liu, Q.Chai, Y.Y.Li, Q.Shen, L.P.Ma, L.N.Zhang, X.Wang, L.Sheng, J.Y.Li, J.Li, and J.K.Shen (2010).
Discovery of novel PTP1B inhibitors with antihyperglycemic activity.
  Acta Pharmacol Sin, 31, 1005-1012.  
19381851 C.O.Kappe, and D.Dallinger (2009).
Controlled microwave heating in modern organic synthesis: highlights from the 2004-2008 literature.
  Mol Divers, 13, 71.  
19810703 D.Vidović, and S.C.Schürer (2009).
Knowledge-based characterization of similarity relationships in the human protein-tyrosine phosphatase family for rational inhibitor design.
  J Med Chem, 52, 6649-6659.  
19380334 J.F.Wang, K.Gong, D.Q.Wei, Y.X.Li, and K.C.Chou (2009).
Molecular dynamics studies on the interactions of PTP1B with inhibitors: from the first phosphate-binding site to the second one.
  Protein Eng Des Sel, 22, 349-355.  
18855890 M.L.Mohler, Y.He, Z.Wu, D.J.Hwang, and D.D.Miller (2009).
Recent and emerging anti-diabetes targets.
  Med Res Rev, 29, 125-195.  
18925939 P.I.Tsai, H.H.Kao, C.Grabbe, Y.T.Lee, A.Ghose, T.T.Lai, K.P.Peng, D.Van Vactor, R.H.Palmer, R.H.Chen, S.R.Yeh, and C.T.Chien (2008).
Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth.
  Neural Develop, 3, 26.  
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