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PDBsum entry 3cpc
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protein ligands Protein-protein interface(s) links
Transferase PDB id
3cpc

 

 

 

 

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Contents
Protein chains
284 a.a. *
262 a.a. *
Ligands
C52 ×2
Waters ×113
* Residue conservation analysis
PDB id:
3cpc
Name: Transferase
Title: Crystal structure of the vegfr2 kinase domain in complex with a pyridone inhibitor
Structure: Vascular endothelial growth factor receptor 2. Chain: a, b. Fragment: protein kinase domain, residues 940-989 deleted. Synonym: vegfr-2, kinase insert domain receptor, protein-tyrosine kinase receptor flk-1, cd309 antigen. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: kdr, flk1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.
Resolution:
2.40Å     R-factor:   0.218     R-free:   0.272
Authors: D.A.Whittington,A.M.Long,P.Rose,Y.Gu,H.Zhao
Key ref: E.Hu et al. (2008). Discovery of aryl aminoquinazoline pyridones as potent, selective, and orally efficacious inhibitors of receptor tyrosine kinase c-Kit. J Med Chem, 51, 3065-3068. PubMed id: 18447379
Date:
31-Mar-08     Release date:   17-Jun-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P35968  (VGFR2_HUMAN) -  Vascular endothelial growth factor receptor 2 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1356 a.a.
284 a.a.*
Protein chain
Pfam   ArchSchema ?
P35968  (VGFR2_HUMAN) -  Vascular endothelial growth factor receptor 2 from Homo sapiens
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1356 a.a.
262 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, B: E.C.2.7.10.1  - receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H+
L-tyrosyl-[protein]
 + ATP
 = O-phospho-L-tyrosyl-[protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    Added reference    
 
 
J Med Chem 51:3065-3068 (2008)
PubMed id: 18447379  
 
 
Discovery of aryl aminoquinazoline pyridones as potent, selective, and orally efficacious inhibitors of receptor tyrosine kinase c-Kit.
E.Hu, A.Tasker, R.D.White, R.K.Kunz, J.Human, N.Chen, R.Bürli, R.Hungate, P.Novak, A.Itano, X.Zhang, V.Yu, Y.Nguyen, Y.Tudor, M.Plant, S.Flynn, Y.Xu, K.L.Meagher, D.A.Whittington, G.Y.Ng.
 
  ABSTRACT  
 
Inhibition of c-Kit has the potential to treat mast cell associated fibrotic diseases. We report the discovery of several aminoquinazoline pyridones that are potent inhibitors of c-Kit with greater than 200-fold selectivity against KDR, p38, Lck, and Src. In vivo efficacy of pyridone 16 by dose-dependent inhibition of histamine release was demonstrated in a rodent pharmacodynamic model of mast cell activation.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19921722 A.Papakyriakou, M.E.Katsarou, M.Belimezi, M.Karpusas, and D.Vourloumis (2010).
Discovery of potent vascular endothelial growth factor receptor-2 inhibitors.
  ChemMedChem, 5, 118-129.  
19053777 I.Kufareva, and R.Abagyan (2008).
Type-II kinase inhibitor docking, screening, and profiling using modified structures of active kinase states.
  J Med Chem, 51, 7921-7932.  
21581454 N.D.Karis, W.A.Loughlin, I.D.Jenkins, and P.C.Healy (2008).
tert-Butyl 2-(3-acetyl-amino-2-oxo-1,2-dihydro-1-pyrid-yl)acetate.
  Acta Crystallogr Sect E Struct Rep Online, 64, o2492-o2493.  
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.

 

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