PDBsum entry 2qdc

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protein ligands links
Hydrolase PDB id
Protein chain
284 a.a. *
PO4 ×2
GOL ×2
Waters ×230
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of the heptp catalytic domain d236a mutant
Structure: Tyrosine-protein phosphatase non-receptor type 7. Chain: a. Fragment: catalytic domain (residues 65-360). Synonym: protein-tyrosine phosphatase lc-ptp, hematopoietic tyrosine phosphatase, heptp. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn7. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.00Å     R-factor:   0.164     R-free:   0.190
Authors: D.A.Critton,A.Tortajada,R.Page
Key ref: D.A.Critton et al. (2008). Structural basis of substrate recognition by hematopoietic tyrosine phosphatase. Biochemistry, 47, 13336-13345. PubMed id: 19053285
20-Jun-07     Release date:   24-Jun-08    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P35236  (PTN7_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 7
360 a.a.
284 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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
Bound ligand (Het Group name = PO4)
corresponds exactly
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  


Biochemistry 47:13336-13345 (2008)
PubMed id: 19053285  
Structural basis of substrate recognition by hematopoietic tyrosine phosphatase.
D.A.Critton, A.Tortajada, G.Stetson, W.Peti, R.Page.
Hematopoietic tyrosine phosphatase (HePTP) is one of three members of the kinase interaction motif (KIM) phosphatase family which also includes STEP and PCPTP1. The KIM-PTPs are characterized by a 15 residue sequence, the KIM, which confers specific high-affinity binding to their only known substrates, the MAP kinases Erk and p38, an interaction which is critical for their ability to regulate processes such as T cell differentiation (HePTP) and neuronal signaling (STEP). The KIM-PTPs are also characterized by a unique set of residues in their PTP substrate binding loops, where 4 of the 13 residues are differentially conserved among the KIM-PTPs as compared to more than 30 other class I PTPs. One of these residues, T106 in HePTP, is either an aspartate or asparagine in nearly every other PTP. Using multiple techniques, we investigate the role of these KIM-PTP specific residues in order to elucidate the molecular basis of substrate recognition by HePTP. First, we used NMR spectroscopy to show that Erk2-derived peptides interact specifically with HePTP at the active site. Next, to reveal the molecular details of this interaction, we solved the high-resolution three-dimensional structures of two distinct HePTP-Erk2 peptide complexes. Strikingly, we were only able to obtain crystals of these transient complexes using a KIM-PTP specific substrate-trapping mutant, in which the KIM-PTP specific residue T106 was mutated to an aspartic acid (T106D). The introduced aspartate side chain facilitates the coordination of the bound peptides, thereby stabilizing the active dephosphorylation complex. These structures establish the essential role of HePTP T106 in restricting HePTP specificity to only those substrates which are able to interact with KIM-PTPs via the KIM (e.g., Erk2, p38). Finally, we describe how this interaction of the KIM is sufficient for overcoming the otherwise weak interaction at the active site of KIM-PTPs.