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PDBsum entry 1l8k
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Hydrolase PDB id
1l8k

 

 

 

 

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Contents
Protein chain
273 a.a. *
Waters ×40
* Residue conservation analysis
PDB id:
1l8k
Name: Hydrolase
Title: T cell protein-tyrosine phosphatase structure
Structure: T-cell protein-tyrosine phosphatase. Chain: a. Synonym: protein-tyrosine phosphatase, non-receptor type 2, tcptp. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.56Å     R-factor:   0.215     R-free:   0.288
Authors: L.F.Iversen
Key ref:
L.F.Iversen et al. (2002). Structure determination of T cell protein-tyrosine phosphatase. J Biol Chem, 277, 19982-19990. PubMed id: 11907034 DOI: 10.1074/jbc.M200567200
Date:
21-Mar-02     Release date:   08-May-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P17706  (PTN2_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 2 from Homo sapiens
Seq:
Struc: 		415 a.a.
273 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.3.48  - protein-tyrosine-phosphatase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate
O-phospho-L-tyrosyl-[protein]
 + H2O
 = L-tyrosyl-[protein]
 + phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Key reference    
 
 
DOI no: 10.1074/jbc.M200567200 J Biol Chem 277:19982-19990 (2002)
PubMed id: 11907034  
 
 
Structure determination of T cell protein-tyrosine phosphatase.
L.F.Iversen, K.B.Moller, A.K.Pedersen, G.H.Peters, A.S.Petersen, H.S.Andersen, S.Branner, S.B.Mortensen, N.P.Moller.
 
  ABSTRACT  
 
Protein-tyrosine phosphatase 1B (PTP1B) has recently received much attention as a potential drug target in type 2 diabetes. This has in particular been spurred by the finding that PTP1B knockout mice show increased insulin sensitivity and resistance to diet-induced obesity. Surprisingly, the highly homologous T cell protein-tyrosine phosphatase (TC-PTP) has received much less attention, and no x-ray structure has been provided. We have previously co-crystallized PTP1B with a number of low molecular weight inhibitors that inhibit TC-PTP with similar efficiency. Unexpectedly, we were not able to co-crystallize TC-PTP with the same set of inhibitors. This seems to be due to a multimerization process where residues 130-132, the DDQ loop, from one molecule is inserted into the active site of the neighboring molecule, resulting in a continuous string of interacting TC-PTP molecules. Importantly, despite the high degree of functional and structural similarity between TC-PTP and PTP1B, we have been able to identify areas close to the active site that might be addressed to develop selective inhibitors of each enzyme.
 
  Selected figure(s)  
 
Figure 2.
Fig. 2. Chemical structures. 		Figure 6.
Fig. 6. Grasp rendering of the PTP1B and TC-PTP surfaces. The two surface areas with structural differences useful for potential selectivity design are indicated by white and yellow circles, respectively. The surface electrostatic potentials are colored in blue for positive charges and in red for negative charges.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2002, 277, 19982-19990) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19290937 K.M.Doody, A.Bourdeau, and M.L.Tremblay (2009).
T-cell protein tyrosine phosphatase is a key regulator in immune cell signaling: lessons from the knockout mouse model and implications in human disease.
  Immunol Rev, 228, 325-341.  
18685809 K.Bharatham, N.Bharatham, Y.J.Kwon, and K.W.Lee (2008).
Molecular dynamics simulation study of PTP1B with allosteric inhibitor and its application in receptor based pharmacophore modeling.
  J Comput Aided Mol Des, 22, 925-933.  
18298793 L.Tabernero, A.R.Aricescu, E.Y.Jones, and S.E.Szedlacsek (2008).
Protein tyrosine phosphatases: structure-function relationships.
  FEBS J, 275, 867-882.  
18412190 S.Mitra, and A.M.Barrios (2008).
Identifying selective protein tyrosine phosphatase substrates and inhibitors from a fluorogenic, combinatorial peptide library.
  Chembiochem, 9, 1216-1219.  
18819921 V.Sangwan, G.N.Paliouras, J.V.Abella, N.Dubé, A.Monast, M.L.Tremblay, and M.Park (2008).
Regulation of the Met receptor-tyrosine kinase by the protein-tyrosine phosphatase 1B and T-cell phosphatase.
  J Biol Chem, 283, 34374-34383.  
17291189 L.I.Pao, K.Badour, K.A.Siminovitch, and B.G.Neel (2007).
Nonreceptor protein-tyrosine phosphatases in immune cell signaling.
  Annu Rev Immunol, 25, 473-523.  
17346049 X.Y.Zhang, and A.C.Bishop (2007).
Site-specific incorporation of allosteric-inhibition sites in a protein tyrosine phosphatase.
  J Am Chem Soc, 129, 3812-3813.  
16769216 E.W.Yue, B.Wayland, B.Douty, M.L.Crawley, E.McLaughlin, A.Takvorian, Z.Wasserman, M.J.Bower, M.Wei, Y.Li, P.J.Ala, L.Gonneville, R.Wynn, T.C.Burn, P.C.Liu, and A.P.Combs (2006).
Isothiazolidinone heterocycles as inhibitors of protein tyrosine phosphatases: synthesis and structure-activity relationships of a peptide scaffold.
  Bioorg Med Chem, 14, 5833-5849.  
16998530 P.D.Simoncic, C.J.McGlade, and M.L.Tremblay (2006).
PTP1B and TC-PTP: novel roles in immune-cell signaling.
  Can J Physiol Pharmacol, 84, 667-675.  
15333922 A.K.Pedersen, G.H.Peters G, K.B.Møller, L.F.Iversen, and J.S.Kastrup (2004).
Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B.
  Acta Crystallogr D Biol Crystallogr, 60, 1527-1534.
PDB code: 1sug
15013940 S.D.Taylor, and B.Hill (2004).
Recent advances in protein tyrosine phosphatase 1B inhibitors.
  Expert Opin Investig Drugs, 13, 199-214.  
12209150 T.O.Johnson, J.Ermolieff, and M.R.Jirousek (2002).
Protein tyrosine phosphatase 1B inhibitors for diabetes.
  Nat Rev Drug Discov, 1, 696-709.  
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. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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