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PDBsum entry 1q7x

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protein links
Hydrolase PDB id
1q7x
Jmol
Contents
Protein chain
108 a.a. *
* Residue conservation analysis
PDB id:
1q7x
Name: Hydrolase
Title: Solution structure of the alternatively spliced pdz2 domain (pdz2b) of ptp-bas (hptp1e)
Structure: Pdz2b domain of ptp-bas (hptp1e). Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptp1e. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: N.Kachel,K.S.Erdmann,W.Kremer,P.Wolff,W.Gronwald,R.Heumann, H.R.Kalbitzer,Structural Proteomics In Europe (Spine)
Key ref:
N.Kachel et al. (2003). Structure determination and ligand interactions of the PDZ2b domain of PTP-Bas (hPTP1E): splicing-induced modulation of ligand specificity. J Mol Biol, 334, 143-155. PubMed id: 14596806 DOI: 10.1016/j.jmb.2003.09.026
Date:
20-Aug-03     Release date:   02-Dec-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q12923  (PTN13_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 13
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
2485 a.a.
108 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 6 residue positions (black crosses)

 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

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2003.09.026 J Mol Biol 334:143-155 (2003)
PubMed id: 14596806  
 
 
Structure determination and ligand interactions of the PDZ2b domain of PTP-Bas (hPTP1E): splicing-induced modulation of ligand specificity.
N.Kachel, K.S.Erdmann, W.Kremer, P.Wolff, W.Gronwald, R.Heumann, H.R.Kalbitzer.
 
  ABSTRACT  
 
Two versions of the PDZ2 domain of the protein tyrosine phosphatase PTP-Bas/human PTP-BL are generated by alternative splicing. The domains differ by the insertion of five amino acid residues and their affinity to the tumour suppressor protein APC. Whereas PDZ2a is able to bind APC in the nanomolar range, PDZ2b shows no apparent interaction with APC. Here the solution structure of the splicing variant of PDZ2 with the insertion has been determined using 2D and 3D heteronuclear NMR experiments. The structural reason for the changed binding specificity is the reorientation of the loop with extra five amino acid residues, which folds back onto beta-strands two and three. In addition the side-chain of Lys32 closes the binding site of the APC binding protein and the two helices, especially alpha-helix 2, change their relative position to the protein core. Consecutively, the binding site is sterically no longer fully accessible. From the NMR-titration studies with a C-terminal APC-peptide the affinity of the peptide with the protein can be estimated as 540(+/-40)microM. The binding site encompasses part of the analogous binding site of PDZ2a as already described previously, yet specific interaction sites are abolished by the insertion of amino acids in PDZ2b. As shown by high-affinity chromatography, GST-PDZ2b and GST-PDZ2a bind to phosphatidylinositol 4,5-bisphosphate (PIP(2)) micelles with a dissociation constant K(D) of 21 microM and 55 microM, respectively. In line with these data PDZ2b binds isolated, dissolved PIP(2) and PIP(3) (phosphatidylinositol 3,4,5-trisphosphate) molecules specifically with a lower K(D) of 230(+/-20)microM as detected by NMR spectroscopy. The binding site could be located by our studies and involves the residues Ile24, Val26, Val70, Asn71, Gly77, Ala78, Glu85, Arg88, Gly91 and Gln92. PIP(2) and PIP(3) binding takes place in the groove of the PDZ domain that is normally part of the APC binding site.
 
  Selected figure(s)  
 
Figure 4.
Figure 4. NOE contacts per residue in PDZ2b of PTP-Bas. The secondary structure is symbolised by arrows (b-strands) and lanyards (a-helices). The position of the insertion is marked in grey.
Figure 6.
Figure 6. NMR structure of PDZ2b. (A) Ribbon representation of the lowest-energy structure of PDZ2b of PTP-Bas. The insertion is highlighted in orange. (B) Backbone representations of the 20 lowest-energy structures from the struc- ture calculation. (C) Electrostatic potential of PDZ2b; negatively charged regions are coloured red, positively charged regions are blue. All molecules are shown in the same orientation. The Figure was prepared using the program MOLMOL. 49
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 334, 143-155) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20972208 H.Hegyi, L.Kalmar, T.Horvath, and P.Tompa (2011).
Verification of alternative splicing variants based on domain integrity, truncation length and intrinsic protein disorder.
  Nucleic Acids Res, 39, 1208-1219.  
20563762 G.Kock, M.Dicks, R.Heumann, K.S.Erdmann, and R.Stoll (2010).
Sequence-specific 1H, 13C, and 15N assignment of the extended PDZ3 domain of the protein tyrosine phosphatase basophil-like PTP-BL.
  Biomol NMR Assign, 4, 199-202.  
19672627 Y.Mita, Y.Yasuda, A.Sakai, H.Yamamoto, S.Toyooka, M.Gunduz, S.Tanabe, Y.Naomoto, M.Ouchida, and K.Shimizu (2010).
Missense polymorphisms of PTPRJ and PTPN13 genes affect susceptibility to a variety of human cancers.
  J Cancer Res Clin Oncol, 136, 249-259.  
18298791 J.den Hertog, A.Ostman, and F.D.Böhmer (2008).
Protein tyrosine phosphatases: regulatory mechanisms.
  FEBS J, 275, 831-847.  
18265946 O.D.Abaan, and J.A.Toretsky (2008).
PTPL1: a large phosphatase with a split personality.
  Cancer Metastasis Rev, 27, 205-214.  
17474715 D.Saro, T.Li, C.Rupasinghe, A.Paredes, N.Caspers, and M.R.Spaller (2007).
A thermodynamic ligand binding study of the third PDZ domain (PDZ3) from the mammalian neuronal protein PSD-95.
  Biochemistry, 46, 6340-6352.  
16462939 S.B.Nabuurs, C.A.Spronk, G.W.Vuister, and G.Vriend (2006).
Traditional biomolecular structure determination by NMR spectroscopy allows for major errors.
  PLoS Comput Biol, 2, e9.  
15961997 E.Mortier, G.Wuytens, I.Leenaerts, F.Hannes, M.Y.Heung, G.Degeest, G.David, and P.Zimmermann (2005).
Nuclear speckles and nucleoli targeting by PIP2-PDZ domain interactions.
  EMBO J, 24, 2556-2565.  
14653806 K.S.Erdmann (2003).
The protein tyrosine phosphatase PTP-Basophil/Basophil-like. Interacting proteins and molecular functions.
  Eur J Biochem, 270, 4789-4798.  
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.