PDBsum entry 1ony

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Hydrolase PDB id
Protein chain
283 a.a. *
Waters ×312
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Oxalyl-aryl-amino benzoic acid inhibitors of ptp1b, compound 17
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.
2.15Å     R-factor:   0.206     R-free:   0.220
Authors: G.Liu,B.G.Szczepankiewicz,Z.Pei,D.A.Janowich,Z.Xin, P.J.Hadjuk,C.Abad-Zapatero,H.Liang,C.W.Hutchins,S.W.Fesik, S.J.Ballaron,M.A.Stashko,T.Lubben,A.K.Mika,B.A.Zinker, J.M.Trevillyan,M.R.Jirousek
Key ref: G.Liu et al. (2003). Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B. J Med Chem, 46, 2093-2103. PubMed id: 12747781 DOI: 10.1021/jm0205696
02-Mar-03     Release date:   20-May-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P18031  (PTN1_HUMAN) -  Tyrosine-protein phosphatase non-receptor type 1
435 a.a.
283 a.a.
Key:    PfamA domain  PfamB 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
+ 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  


DOI no: 10.1021/jm0205696 J Med Chem 46:2093-2103 (2003)
PubMed id: 12747781  
Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B.
G.Liu, B.G.Szczepankiewicz, Z.Pei, D.A.Janowick, Z.Xin, P.J.Hajduk, C.Abad-Zapatero, H.Liang, C.W.Hutchins, S.W.Fesik, S.J.Ballaron, M.A.Stashko, T.Lubben, A.K.Mika, B.A.Zinker, J.M.Trevillyan, M.R.Jirousek.
Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20205445 R.G.Coleman, and K.A.Sharp (2010).
Protein pockets: inventory, shape, and comparison.
  J Chem Inf Model, 50, 589-603.  
18855890 M.L.Mohler, Y.He, Z.Wu, D.J.Hwang, and D.D.Miller (2009).
Recent and emerging anti-diabetes targets.
  Med Res Rev, 29, 125-195.  
19240079 N.J.Beresford, D.Mulhearn, B.Szczepankiewicz, G.Liu, M.E.Johnson, A.Fordham-Skelton, C.Abad-Zapatero, J.S.Cavet, and L.Tabernero (2009).
Inhibition of MptpB phosphatase from Mycobacterium tuberculosis impairs mycobacterial survival in macrophages.
  J Antimicrob Chemother, 63, 928-936.  
17506119 C.A.Albarracin, B.C.Fuqua, J.L.Evans, and I.D.Goldfine (2008).
Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes.
  Diabetes Metab Res Rev, 24, 41-51.  
17275735 H.Zhao (2007).
Scaffold selection and scaffold hopping in lead generation: a medicinal chemistry perspective.
  Drug Discov Today, 12, 149-155.  
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.  
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.  
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
16441232 O.Boss, and N.Bergenhem (2006).
Adipose targets for obesity drug development.
  Expert Opin Ther Targets, 10, 119-134.  
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.  
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.