PDBsum entry 1zc0

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Hydrolase PDB id
Protein chain
286 a.a. *
Waters ×286
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of human hematopoietic tyrosine phosphatas catalytic domain
Structure: Tyrosine-protein phosphatase, non-receptor type 7 chain: a. Fragment: catalytic phosphatase domain. Synonym: protein-tyrosine phosphatase lc-ptp, hematopoietic tyrosine phosphatase, heptp. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn7. Expressed in: escherichia coli. Expression_system_taxid: 562
1.85Å     R-factor:   0.163     R-free:   0.186
Authors: R.Page,T.Mustelin
Key ref:
T.Mustelin et al. (2005). Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site. J Mol Biol, 354, 150-163. PubMed id: 16226275 DOI: 10.1016/j.jmb.2005.09.049
09-Apr-05     Release date:   06-Dec-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P35236  (PTN7_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 7
360 a.a.
286 a.a.
Key:    PfamA 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
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  


DOI no: 10.1016/j.jmb.2005.09.049 J Mol Biol 354:150-163 (2005)
PubMed id: 16226275  
Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site.
T.Mustelin, L.Tautz, R.Page.
Hematopoietic tyrosine phosphatase (HePTP) is a 38kDa class I non-receptor protein tyrosine phosphatase (PTP) that is strongly expressed in T cells. It is composed of a C-terminal classical PTP domain (residues 44-339) and a short N-terminal extension (residues 1-43) that functions to direct HePTP to its physiological substrates. Moreover, HePTP is a member of a recently identified family of PTPs that has a major role in regulating the activity and translocation of the MAP kinases Erk and p38. HePTP binds Erk and p38 via a short, highly conserved motif in its N terminus, termed the kinase interaction motif (KIM). Association of HePTP with Erk via the KIM results in an unusual, reciprocal interaction between the two proteins. First, Erk phosphorylates HePTP at residues Thr45 and Ser72. Second, HePTP dephosphorylates Erk at PTyr185. In order to gain further insight into the interaction of HePTP with Erk, we determined the structure of the PTP catalytic domain of HePTP, residues 44-339. The HePTP catalytic phosphatase domain displays the classical PTP1B fold and superimposes well with PTP-SL, the first KIM-containing phosphatase solved to high resolution. In contrast to the PTP-SL structure, however, HePTP crystallized with a well-ordered phosphate ion bound at the active site. This resulted in the closure of the catalytically important WPD loop, and thus, HePTP represents the first KIM-containing phosphatase solved in the closed conformation. Finally, using this structure of the HePTP catalytic domain, we show that both the phosphorylation of HePTP at Thr45 and Ser72 by Erk2 and the dephosphorylation of Erk2 at Tyr185 by HePTP require significant conformational changes in both proteins.
  Selected figure(s)  
Figure 1.
Figure 1. Cartoon representation and structure of HePTP. (a) Cartoon representation of HePTP domain structure. The N-terminal domain of HePTP (cyan) includes the kinase interaction motif (KIM, pink, residues 15-30) while the C-terminal domain includes the PTP domain (orange, residues 44-339). The HePTP domain solved to high resolution is that of the PTP catalytic domain (residues 44-339). (b) Secondary structure of HePTP catalytic domain. Secondary structure elements numbered as for PTP1B. The bound phosphate ion is shown as a space-filling model in red. Four residues of the loop connecting b-strand 4 to b-strand 7 (b-strands 5 and 6 are not present in HePTP) could not be modeled and are presumably disordered. (c) PTP motifs in HePTP. The HePTP WPD loop is shown in cyan, the PTP motif phosphate-binding loop in magenta, the Q-loop in green and a-helix a0 in coral.21
Figure 2.
Figure 2. The HePTP active site. (a) Electron density for the bound phosphate moiety. Magenta, sA-weighted 2mF[o] -DF[c] map contoured at 1.5s; red, sA-weighted mF[o] -DF[c] omit map contoured at 4.5s. Electron density maps clearly illustrate the tetrahedral-shaped density of the phosphate ion. (b) Reorientation of the WPD loop upon phosphate binding. The superposition of the active site of HePTP (orange) and apo-PTP-SL (blue) is shown. The binding of the phosphate ion leads to the rotation of the Arg276 side-chain about the Cg atom, the closing of the WPD loop and the subsequent reorientation of the catalytic acid Asp236 in HePTP relative to PTP-SL. The HePTP and PTP-SL structures have been superimposed over 253 residues with an rmsd of 0.72 Å. (c) Dual conformations of active site residues His237 and Gln314. The hydrogen bonding network of the bound phosphate ion is shown. Residues from the WPD loop (purple), PTP motif phosphate-binding loop (coral) and Q-loop (cyan) interact with the bound phosphate. Water molecules are shown as stars. The dual conformations of His237 (WPD loop) and Gln314 (Q loop) are shown.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 354, 150-163) copyright 2005.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20659529 R.R.Ruela-de-Sousa, K.C.Queiroz, M.P.Peppelenbosch, and G.M.Fuhler (2010).
Reversible phosphorylation in haematological malignancies: potential role for protein tyrosine phosphatases in treatment?
  Biochim Biophys Acta, 1806, 287-303.  
19047375 J.W.McAlees, and V.M.Sanders (2009).
Hematopoietic protein tyrosine phosphatase mediates beta2-adrenergic receptor-induced regulation of p38 mitogen-activated protein kinase in B lymphocytes.
  Mol Cell Biol, 29, 675-686.  
18598228 A.Muise, and D.Rotin (2008).
Apical junction complex proteins and ulcerative colitis: a focus on the PTPRS gene.
  Expert Rev Mol Diagn, 8, 465-477.  
19053285 D.A.Critton, A.Tortajada, G.Stetson, W.Peti, and R.Page (2008).
Structural basis of substrate recognition by hematopoietic tyrosine phosphatase.
  Biochemistry, 47, 13336-13345.
PDB codes: 2hvl 2qdc 2qdm 2qdp 3d42 3d44
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.  
18678493 X.Y.Zhang, V.L.Chen, M.S.Rosen, E.R.Blair, A.M.Lone, and A.C.Bishop (2008).
Allele-specific inhibition of divergent protein tyrosine phosphatases with a single small molecule.
  Bioorg Med Chem, 16, 8090-8097.  
17532515 A.C.Bishop, X.Y.Zhang, and A.M.Lone (2007).
Generation of inhibitor-sensitive protein tyrosine phosphatases via active-site mutations.
  Methods, 42, 278-288.  
17596826 A.K.Nordle, P.Rios, A.Gaulton, R.Pulido, T.K.Attwood, and L.Tabernero (2007).
Functional assignment of MAPK phosphatase domains.
  Proteins, 69, 19-31.  
16919785 A.J.Barr, and S.Knapp (2006).
MAPK-specific tyrosine phosphatases: new targets for drug discovery?
  Trends Pharmacol Sci, 27, 525-530.  
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 codes are shown on the right.