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PDBsum entry 2rgp

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protein ligands links
Transferase PDB id
2rgp
Jmol
Contents
Protein chain
284 a.a. *
Ligands
PO4 ×2
HYZ
Waters ×85
* Residue conservation analysis
PDB id:
2rgp
Name: Transferase
Title: Structure of egfr in complex with hydrazone, a potent dual inhibitor
Structure: Epidermal growth factor receptor. Chain: a. Fragment: residues 702-1016. Synonym: receptor tyrosine-protein kinase erbb-1. Engineered: yes
Source: Homo sapiens. Human. Strain: human strains undefined. Gene: egfr, erbb1. Expressed in: spodoptera frugiperda.
Resolution:
2.00Å     R-factor:   0.228     R-free:   0.268
Authors: M.C.Abad
Key ref: G.Xu et al. (2008). 4-Amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones as potent ErbB-2/EGFR dual kinase inhibitors. Bioorg Med Chem Lett, 18, 4615-4619. PubMed id: 18653333 DOI: 10.1016/j.bmcl.2008.07.020
Date:
04-Oct-07     Release date:   26-Aug-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P00533  (EGFR_HUMAN) -  Epidermal growth factor receptor
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1210 a.a.
284 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.10.1  - Receptor protein-tyrosine kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
ATP
+ [protein]-L-tyrosine
= ADP
+ [protein]-L-tyrosine phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     protein phosphorylation   1 term 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2008.07.020 Bioorg Med Chem Lett 18:4615-4619 (2008)
PubMed id: 18653333  
 
 
4-Amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones as potent ErbB-2/EGFR dual kinase inhibitors.
G.Xu, M.C.Abad, P.J.Connolly, M.P.Neeper, G.T.Struble, B.A.Springer, S.L.Emanuel, N.Pandey, R.H.Gruninger, M.Adams, S.Moreno-Mazza, A.R.Fuentes-Pesquera, S.A.Middleton.
 
  ABSTRACT  
 
Members of a novel class of 4-amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones were identified as potent dual ErbB-2/EGFR kinase inhibitors using concept-guided design approach. These compounds inhibited the growth of ErbB-2 over-expressing human tumor cell lines (BT474, N87, and SK-BR-3) in vitro. Compound 15 emerged as a key lead and showed significant ability to inhibit growth factor-induced receptor phosphorylation in SK-BR-3 cells (IC(50)=54 nM) and cellular proliferation in vitro (IC(50)=14, 58, and 58 nM for BT474, N87, and SK-BR-3 respectively). The X-ray co-crystal structure of EGFR with a close analog (17) was determined and validated our design rationale.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21052789 L.Kong, Z.Deng, H.Shen, and Y.Zhang (2011).
Src family kinase inhibitor PP2 efficiently inhibits cervical cancer cell proliferation through down-regulating phospho-Src-Y416 and phospho-EGFR-Y1173.
  Mol Cell Biochem, 348, 11-19.  
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