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PDBsum entry 1een

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protein ligands metals links
Hydrolase PDB id
1een
Jmol
Contents
Protein chain
299 a.a. *
Ligands
ALA-ASP-PBF-PTR-
LEU-ILE-PRO
ACY ×2
Metals
_MG
Waters ×300
* Residue conservation analysis
PDB id:
1een
Name: Hydrolase
Title: Crystal structure of protein tyrosine phosphatase 1b complexed with acetyl-d-a-d-bpa-ptyr-l-i-p-q-q-g
Structure: Protein tyrosine phosphatase 1b. Chain: a. Fragment: residues 1-321. Synonym: ptp1b. Engineered: yes. Mutation: yes. Ala-asp-pbf-ptr-leu-ile-pro. Chain: b. Engineered: yes.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Synthetic: yes
Biol. unit: Dimer (from PQS)
Resolution:
1.90Å     R-factor:   0.188     R-free:   0.217
Authors: Y.A.Puius,Y.Zhao,S.C.Almo,Z.Y.Zhang
Key ref:
M.Sarmiento et al. (2000). Structural basis of plasticity in protein tyrosine phosphatase 1B substrate recognition. Biochemistry, 39, 8171-8179. PubMed id: 10889023 DOI: 10.1021/bi000319w
Date:
01-Feb-00     Release date:   01-Feb-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1
Seq:
Struc:
435 a.a.
299 a.a.*
Key:    PfamA domain  PfamB 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
Bound ligand (Het Group name = PTR)
matches with 76.00% similarity
+ 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: 10.1021/bi000319w Biochemistry 39:8171-8179 (2000)
PubMed id: 10889023  
 
 
Structural basis of plasticity in protein tyrosine phosphatase 1B substrate recognition.
M.Sarmiento, Y.A.Puius, S.W.Vetter, Y.F.Keng, L.Wu, Y.Zhao, D.S.Lawrence, S.C.Almo, Z.Y.Zhang.
 
  ABSTRACT  
 
Protein tyrosine phosphatase 1B (PTP1B) displays a preference for peptides containing acidic as well as aromatic/aliphatic residues immediately NH(2)-terminal to phosphotyrosine. The structure of PTP1B bound with DADEpYL-NH(2) (EGFR(988)(-)(993)) offers a structural explanation for PTP1B's preference for acidic residues [Jia, Z., Barford, D., Flint, A. J., and Tonks, N. K. (1995) Science 268, 1754-1758]. We report here the crystal structures of PTP1B in complex with Ac-ELEFpYMDYE-NH(2) (PTP1B.Con) and Ac-DAD(Bpa)pYLIPQQG (PTP1B.Bpa) determined to 1.8 and 1.9 A resolution, respectively. A structural analysis of PTP1B.Con and PTP1B.Bpa shows how aromatic/aliphatic residues at the -1 and -3 positions of peptide substrates are accommodated by PTP1B. A comparison of the structures of PTP1B.Con and PTP1B.Bpa with that of PTP1B.EGFR(988)(-)(993) reveals the structural basis for the plasticity of PTP1B substrate recognition. PTP1B is able to bind phosphopeptides by utilizing common interactions involving the aromatic ring and phosphate moiety of phosphotyrosine itself, two conserved hydrogen bonds between the Asp48 carboxylate side chain and the main chain nitrogens of the pTyr and residue 1, and a third between the main chain nitrogen of Arg47 and the main chain carbonyl of residue -2. The ability of PTP1B to accommodate both acidic and hydrophobic residues immediately NH(2)-terminal to pTyr appears to be conferred upon PTP1B by a single residue, Arg47. Depending on the nature of the NH(2)-terminal amino acids, the side chain of Arg47 can adopt one of two different conformations, generating two sets of distinct peptide binding surfaces. When an acidic residue is positioned at position -1, a preference for a second acidic residue is also observed at position -2. However, when a large hydrophobic group occupies position -1, Arg47 adopts a new conformation so that it can participate in hydrophobic interactions with both positions -1 and -3.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
22562138 L.Liu, S.C.Kohout, Q.Xu, S.Müller, C.R.Kimberlin, E.Y.Isacoff, and D.L.Minor (2012).
A glutamate switch controls voltage-sensitive phosphatase function.
  Nat Struct Mol Biol, 19, 633-641.
PDB codes: 3v0d 3v0e 3v0f 3v0g 3v0h 3v0i 3v0j
21123182 E.Ferrari, M.Tinti, S.Costa, S.Corallino, A.P.Nardozza, A.Chatraryamontri, A.Ceol, G.Cesareni, and L.Castagnoli (2011).
Identification of new substrates of the protein-tyrosine phosphatase PTP1B by Bayesian integration of proteome evidence.
  J Biol Chem, 286, 4173-4185.  
19197921 J.Jiang, D.Zeng, and S.Li (2009).
Photogenerated quinone methides as protein affinity labeling reagents.
  Chembiochem, 10, 635-638.  
19351884 N.Krishnan, D.G.Jeong, S.K.Jung, S.E.Ryu, A.Xiao, C.D.Allis, S.J.Kim, and N.K.Tonks (2009).
Dephosphorylation of the C-terminal Tyrosyl Residue of the DNA Damage-related Histone H2A.X Is Mediated by the Protein Phosphatase Eyes Absent.
  J Biol Chem, 284, 16066-16070.  
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
18245086 R.Agarwal, S.K.Burley, and S.Swaminathan (2008).
Structure of human dual specificity protein phosphatase 23, VHZ, enzyme-substrate/product complex.
  J Biol Chem, 283, 8946-8953.
PDB code: 2img
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.  
17173287 H.M.Chu, and A.H.Wang (2007).
Enzyme-substrate interactions revealed by the crystal structures of the archaeal Sulfolobus PTP-fold phosphatase and its phosphopeptide complexes.
  Proteins, 66, 996.
PDB codes: 2dxp 2i6i 2i6j 2i6m 2i6o 2i6p
17543532 R.Maccari, P.Paoli, R.Ottanà, M.Jacomelli, R.Ciurleo, G.Manao, T.Steindl, T.Langer, M.G.Vigorita, and G.Camici (2007).
5-Arylidene-2,4-thiazolidinediones as inhibitors of protein tyrosine phosphatases.
  Bioorg Med Chem, 15, 5137-5149.  
15139811 D.A.Erlanson, J.A.Wells, and A.C.Braisted (2004).
Tethering: fragment-based drug discovery.
  Annu Rev Biophys Biomol Struct, 33, 199-223.  
15185380 M.Saviano, R.Improta, E.Benedetti, B.Carrozzini, G.L.Cascarano, C.Didierjean, C.Toniolo, and M.Crisma (2004).
Benzophenone photophore flexibility and proximity: molecular and crystal-state structure of a Bpa-containing trichogin dodecapeptide analogue.
  Chembiochem, 5, 541-544.  
14578355 S.Wälchli, X.Espanel, A.Harrenga, M.Rossi, G.Cesareni, and R.H.van Huijsduijnen (2004).
Probing protein-tyrosine phosphatase substrate specificity using a phosphotyrosine-containing phage library.
  J Biol Chem, 279, 311-318.  
15466470 Z.Huang, B.Zhou, and Z.Y.Zhang (2004).
Molecular determinants of substrate recognition in hematopoietic protein-tyrosine phosphatase.
  J Biol Chem, 279, 52150-52159.  
12888560 F.Liang, Z.Huang, S.Y.Lee, J.Liang, M.I.Ivanov, A.Alonso, J.B.Bliska, D.S.Lawrence, T.Mustelin, and Z.Y.Zhang (2003).
Aurintricarboxylic acid blocks in vitro and in vivo activity of YopH, an essential virulent factor of Yersinia pestis, the agent of plague.
  J Biol Chem, 278, 41734-41741.  
12547827 J.P.Sun, A.A.Fedorov, S.Y.Lee, X.L.Guo, K.Shen, D.S.Lawrence, S.C.Almo, and Z.Y.Zhang (2003).
Crystal structure of PTP1B complexed with a potent and selective bidentate inhibitor.
  J Biol Chem, 278, 12406-12414.
PDB codes: 1n6w 1pxh
12810712 J.P.Sun, L.Wu, A.A.Fedorov, S.C.Almo, and Z.Y.Zhang (2003).
Crystal structure of the Yersinia protein-tyrosine phosphatase YopH complexed with a specific small molecule inhibitor.
  J Biol Chem, 278, 33392-33399.
PDB code: 1pa9
12556216 Z.Y.Zhang, and S.Y.Lee (2003).
PTP1B inhibitors as potential therapeutics in the treatment of type 2 diabetes and obesity.
  Expert Opin Investig Drugs, 12, 223-233.  
12082107 B.Zhou, Z.X.Wang, Y.Zhao, D.L.Brautigan, and Z.Y.Zhang (2002).
The specificity of extracellular signal-regulated kinase 2 dephosphorylation by protein phosphatases.
  J Biol Chem, 277, 31818-31825.  
11805096 D.F.McCain, I.E.Catrina, A.C.Hengge, and Z.Y.Zhang (2002).
The catalytic mechanism of Cdc25A phosphatase.
  J Biol Chem, 277, 11190-11200.  
12119018 E.Asante-Appiah, S.Patel, C.Dufresne, P.Roy, Q.Wang, V.Patel, R.W.Friesen, C.Ramachandran, J.W.Becker, Y.Leblanc, B.P.Kennedy, and G.Scapin (2002).
The structure of PTP-1B in complex with a peptide inhibitor reveals an alternative binding mode for bisphosphonates.
  Biochemistry, 41, 9043-9051.
PDB code: 1lqf
12193602 X.L.Guo, K.Shen, F.Wang, D.S.Lawrence, and Z.Y.Zhang (2002).
Probing the molecular basis for potent and selective protein-tyrosine phosphatase 1B inhibition.
  J Biol Chem, 277, 41014-41022.  
11807171 Z.Y.Zhang (2002).
Protein tyrosine phosphatases: structure and function, substrate specificity, and inhibitor development.
  Annu Rev Pharmacol Toxicol, 42, 209-234.  
12191622 Z.Y.Zhang, B.Zhou, and L.Xie (2002).
Modulation of protein kinase signaling by protein phosphatases and inhibitors.
  Pharmacol Ther, 93, 307-317.  
11468356 G.Scapin, S.Patel, V.Patel, B.Kennedy, and E.Asante-Appiah (2001).
The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just an S --> O change.
  Protein Sci, 10, 1596-1605.
PDB code: 1i57
11585896 J.N.Andersen, O.H.Mortensen, G.H.Peters, P.G.Drake, L.F.Iversen, O.H.Olsen, P.G.Jansen, H.S.Andersen, N.K.Tonks, and N.P.Møller (2001).
Structural and evolutionary relationships among protein tyrosine phosphatase domains.
  Mol Cell Biol, 21, 7117-7136.  
11584002 K.Shen, Y.F.Keng, L.Wu, X.L.Guo, D.S.Lawrence, and Z.Y.Zhang (2001).
Acquisition of a specific and potent PTP1B inhibitor from a novel combinatorial library and screening procedure.
  J Biol Chem, 276, 47311-47319.  
11470605 Z.Y.Zhang (2001).
Protein tyrosine phosphatases: prospects for therapeutics.
  Curr Opin Chem Biol, 5, 416-423.  
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.