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PDBsum entry 2bv5

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Hydrolase PDB id
2bv5
Jmol
Contents
Protein chain
282 a.a. *
Ligands
SO4
GOL
Waters ×271
* Residue conservation analysis
PDB id:
2bv5
Name: Hydrolase
Title: Crystal structure of the human protein tyrosine phosphatase ptpn5 at 1.8a resolution
Structure: Tyrosine-protein phosphatase, non-receptor type 5 chain: a. Fragment: catalytic domain, residues 256-537. Synonym: human protein tyrosine phosphatase ptpn5. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: brain. Expressed in: escherichia coli. Expression_system_taxid: 511693. Expression_system_cell_line: de3.
Resolution:
1.80Å     R-factor:   0.166     R-free:   0.201
Authors: J.E.Debreczeni,A.J.Barr,J.Eswaran,C.Smee,N.Burgess,O.Gileadi F.Von Delft,M.Sundstrom,C.Arrowsmith,A.Edwards,S.Knapp
Key ref: J.Eswaran et al. (2006). Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases. Biochem J, 395, 483-491. PubMed id: 16441242 DOI: 10.1042/BJ20051931
Date:
22-Jun-05     Release date:   14-Jul-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P54829  (PTN5_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 5
Seq:
Struc:
 
Seq:
Struc:
565 a.a.
282 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     dephosphorylation   2 terms 
  Biochemical function     phosphatase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1042/BJ20051931 Biochem J 395:483-491 (2006)
PubMed id: 16441242  
 
 
Crystal structures and inhibitor identification for PTPN5, PTPRR and PTPN7: a family of human MAPK-specific protein tyrosine phosphatases.
J.Eswaran, J.P.von Kries, B.Marsden, E.Longman, J.E.Debreczeni, E.Ugochukwu, A.Turnbull, W.H.Lee, S.Knapp, A.J.Barr.
 
  ABSTRACT  
 
Protein tyrosine phosphatases PTPN5, PTPRR and PTPN7 comprise a family of phosphatases that specifically inactivate MAPKs (mitogen-activated protein kinases). We have determined high-resolution structures of all of the human family members, screened them against a library of 24000 compounds and identified two classes of inhibitors, cyclopenta[c]quinolinecarboxylic acids and 2,5-dimethylpyrrolyl benzoic acids. Comparative structural analysis revealed significant differences within this conserved family that could be explored for the design of selective inhibitors. PTPN5 crystallized, in two distinct crystal forms, with a sulphate ion in close proximity to the active site and the WPD (Trp-Pro-Asp) loop in a unique conformation, not seen in other PTPs, ending in a 3(10)-helix. In the PTPN7 structure, the WPD loop was in the closed conformation and part of the KIM (kinase-interaction motif) was visible, which forms an N-terminal aliphatic helix with the phosphorylation site Thr66 in an accessible position. The WPD loop of PTPRR was open; however, in contrast with the structure of its mouse homologue, PTPSL, a salt bridge between the conserved lysine and aspartate residues, which has been postulated to confer a more rigid loop structure, thereby modulating activity in PTPSL, does not form in PTPRR. One of the identified inhibitor scaffolds, cyclopenta[c]quinoline, was docked successfully into PTPRR, suggesting several possibilities for hit expansion. The determined structures together with the established SAR (structure-activity relationship) propose new avenues for the development of selective inhibitors that may have therapeutic potential for treating neurodegenerative diseases in the case of PTPRR or acute myeloblastic leukaemia targeting PTPN7.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20733586 M.F.Champy, L.Le Voci, M.Selloum, L.B.Peterson, A.M.Cumiskey, and D.Blom (2011).
Reduced body weight in male Tspan8-deficient mice.
  Int J Obes (Lond), 35, 605-617.  
19489729 A.Edwards (2009).
Large-scale structural biology of the human proteome.
  Annu Rev Biochem, 78, 541-568.  
19167335 A.J.Barr, E.Ugochukwu, W.H.Lee, O.N.King, P.Filippakopoulos, I.Alfano, P.Savitsky, N.A.Burgess-Brown, S.Müller, and S.Knapp (2009).
Large-scale structural analysis of the classical human protein tyrosine phosphatome.
  Cell, 136, 352-363.
PDB codes: 2ahs 2b49 2cfv 2cjz 2gjt 2h4v 2i75 2jjd 2nlk 2nz6 2oc3 2ooq 2p6x 2pa5 2qep 3b7o
19424502 M.C.Balasu, L.N.Spiridon, S.Miron, C.T.Craescu, A.J.Scheidig, A.J.Petrescu, and S.E.Szedlacsek (2009).
Interface analysis of the complex between ERK2 and PTP-SL.
  PLoS ONE, 4, e5432.  
20015382 M.Menigatti, E.Cattaneo, J.Sabates-Bellver, V.V.Ilinsky, P.Went, F.Buffoli, V.E.Marquez, J.Jiricny, and G.Marra (2009).
The protein tyrosine phosphatase receptor type R gene is an early and frequent target of silencing in human colorectal tumorigenesis.
  Mol Cancer, 8, 124.  
19530895 P.A.Johnston, C.A.Foster, M.B.Tierno, T.Y.Shun, S.N.Shinde, W.D.Paquette, K.M.Brummond, P.Wipf, and J.S.Lazo (2009).
Cdc25B dual-specificity phosphatase inhibitors identified in a high-throughput screen of the NIH compound library.
  Assay Drug Dev Technol, 7, 250-265.  
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
18282486 J.Weigelt, L.D.McBroom-Cerajewski, M.Schapira, Y.Zhao, C.H.Arrowsmith, and C.H.Arrowmsmith (2008).
Structural genomics and drug discovery: all in the family.
  Curr Opin Chem Biol, 12, 32-39.  
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.  
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.  
17638532 P.A.Johnston, C.A.Foster, T.Y.Shun, J.J.Skoko, S.Shinde, P.Wipf, and J.S.Lazo (2007).
Development and implementation of a 384-well homogeneous fluorescence intensity high-throughput screening assay to identify mitogen-activated protein kinase phosphatase-1 dual-specificity protein phosphatase inhibitors.
  Assay Drug Dev Technol, 5, 319-332.  
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.