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PDBsum entry 3o4u

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protein ligands links
Hydrolase PDB id
3o4u
Jmol
Contents
Protein chain
276 a.a. *
Ligands
TLA
SRT
GOL ×2
Waters ×143
* Residue conservation analysis
PDB id:
3o4u
Name: Hydrolase
Title: Crystal structure of heptp with an atypically open wpd loop
Structure: Tyrosine-protein phosphatase non-receptor type 7. Chain: a. Fragment: unp 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: 469008.
Resolution:
2.25Å     R-factor:   0.193     R-free:   0.243
Authors: D.A.Critton,R.Page
Key ref: D.A.Critton et al. (2011). Visualizing active-site dynamics in single crystals of HePTP: opening of the WPD loop involves coordinated movement of the E loop. J Mol Biol, 405, 619-629. PubMed id: 21094165 DOI: 10.1016/j.jmb.2010.11.020
Date:
27-Jul-10     Release date:   24-Nov-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P35236  (PTN7_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 7
Seq:
Struc:
360 a.a.
276 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.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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     dephosphorylation   2 terms 
  Biochemical function     phosphatase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2010.11.020 J Mol Biol 405:619-629 (2011)
PubMed id: 21094165  
 
 
Visualizing active-site dynamics in single crystals of HePTP: opening of the WPD loop involves coordinated movement of the E loop.
D.A.Critton, L.Tautz, R.Page.
 
  ABSTRACT  
 
Phosphotyrosine hydrolysis by protein tyrosine phosphatases (PTPs) involves substrate binding by the PTP loop and closure over the active site by the WPD loop. The E loop, located immediately adjacent to the PTP and WPD loops, is conserved among human PTPs in both sequence and structure, yet the role of this loop in substrate binding and catalysis is comparatively unexplored. Hematopoietic PTP (HePTP) is a member of the kinase interaction motif (KIM) PTP family. Compared to other PTPs, KIM-PTPs have E loops that are unique in both sequence and structure. In order to understand the role of the E loop in the transition between the closed state and the open state of HePTP, we identified a novel crystal form of HePTP that allowed the closed-state-to-open-state transition to be observed within a single crystal form. These structures, which include the first structure of the HePTP open state, show that the WPD loop adopts an 'atypically open' conformation and, importantly, that ligands can be exchanged at the active site, which is critical for HePTP inhibitor development. These structures also show that tetrahedral oxyanions bind at a novel secondary site and function to coordinate the PTP, WPD, and E loops. Finally, using both structural and kinetic data, we reveal a novel role for E-loop residue Lys182 in enhancing HePTP catalytic activity through its interaction with Asp236 of the WPD loop, providing the first evidence for the coordinated dynamics of the WPD and E loops in the catalytic cycle, which, as we show, is relevant to multiple PTP families.