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PDBsum entry 1nz7

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Hydrolase PDB id
1nz7
Jmol
Contents
Protein chain
283 a.a. *
Ligands
901
Waters ×215
* Residue conservation analysis
PDB id:
1nz7
Name: Hydrolase
Title: Potent, selective inhibitors of protein tyrosine phosphatase 1b using a second phosphotyrosine binding site, complexed with compound 19.
Structure: Protein-tyrosine phosphatase, non-receptor type 1. Chain: a. Fragment: ptp1b catalytic domain. Synonym: protein-tyrosine phosphatase 1b, ptp-1b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: ptpn1 or ptp1b. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.40Å     R-factor:   0.194     R-free:   0.217
Authors: Z.Xin,T.K.Oost,C.Abad-Zapatero,P.J.Hajduk,Z.Pei, B.G.Szczepankiewicz,C.W.Hutchins,S.J.Ballaron,M.A.Stashko, T.Lubben,J.M.Trevillyan,M.R.Jirousek,G.Liu
Key ref: Z.Xin et al. (2003). Potent, selective inhibitors of protein tyrosine phosphatase 1B. Bioorg Med Chem Lett, 13, 1887-1890. PubMed id: 12749891 DOI: 10.1016/S0960-894X(03)00302-0
Date:
16-Feb-03     Release date:   20-May-03    
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.
283 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 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/S0960-894X(03)00302-0 Bioorg Med Chem Lett 13:1887-1890 (2003)
PubMed id: 12749891  
 
 
Potent, selective inhibitors of protein tyrosine phosphatase 1B.
Z.Xin, T.K.Oost, C.Abad-Zapatero, P.J.Hajduk, Z.Pei, B.G.Szczepankiewicz, C.W.Hutchins, S.J.Ballaron, M.A.Stashko, T.Lubben, J.M.Trevillyan, M.R.Jirousek, G.Liu.
 
  ABSTRACT  
 
We have previously reported a novel series of oxalyl-aryl-amino benzoic acid-based, catalytic site-directed, competitive, reversible protein tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  19238234 N.Verma, M.Mittal, and R.K.Verma (2008).
Docking of oxalyl aryl amino benzoic acid derivatives into PTP1B.
  Bioinformation, 3, 83-88.  
17039461 S.Lee, and Q.Wang (2007).
Recent development of small molecular specific inhibitor of protein tyrosine phosphatase 1B.
  Med Res Rev, 27, 553-573.  
16580603 A.J.Orry, R.A.Abagyan, and C.N.Cavasotto (2006).
Structure-based development of target-specific compound libraries.
  Drug Discov Today, 11, 261-266.  
16407290 E.Asante-Appiah, S.Patel, C.Desponts, J.M.Taylor, C.Lau, C.Dufresne, M.Therien, R.Friesen, J.W.Becker, Y.Leblanc, B.P.Kennedy, and G.Scapin (2006).
Conformation-assisted inhibition of protein-tyrosine phosphatase-1B elicits inhibitor selectivity over T-cell protein-tyrosine phosphatase.
  J Biol Chem, 281, 8010-8015.
PDB codes: 2fjm 2fjn
15013940 S.D.Taylor, and B.Hill (2004).
Recent advances in protein tyrosine phosphatase 1B inhibitors.
  Expert Opin Investig Drugs, 13, 199-214.  
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.