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PDBsum entry 3bea

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protein ligands links
Transferase PDB id
3bea
Jmol
Contents
Protein chain
310 a.a. *
Ligands
SO4 ×3
IXH
Waters ×169
* Residue conservation analysis
PDB id:
3bea
Name: Transferase
Title: Cfms tyrosine kinase (tie2 kid) in complex with a pyrimidinopyridone inhibitor
Structure: Macrophage colony-stimulating factor 1 receptor. Chain: a. Synonym: csf-1-r, fms proto-oncogene, c-fms, cd115 antigen. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Gene: csf1r, fms. Expressed in: spodoptera frugiperda
Resolution:
2.02Å     R-factor:   0.193     R-free:   0.230
Authors: C.Schubert
Key ref: H.Huang et al. (2008). Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors. Bioorg Med Chem Lett, 18, 2355-2361. PubMed id: 18342505 DOI: 10.1016/j.bmcl.2008.02.070
Date:
16-Nov-07     Release date:   15-Jul-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07333  (CSF1R_HUMAN) -  Macrophage colony-stimulating factor 1 receptor
Seq:
Struc:
 
Seq:
Struc:
972 a.a.
310 a.a.*
Protein chain
Pfam   ArchSchema ?
Q02763  (TIE2_HUMAN) -  Angiopoietin-1 receptor
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1124 a.a.
310 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 188 residue positions (black crosses)

 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!
  Cellular component     membrane   1 term 
  Biological process     transmembrane receptor protein tyrosine kinase signaling pathway   2 terms 
  Biochemical function     transferase activity, transferring phosphorus-containing groups     5 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.bmcl.2008.02.070 Bioorg Med Chem Lett 18:2355-2361 (2008)
PubMed id: 18342505  
 
 
Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors.
H.Huang, D.A.Hutta, H.Hu, R.L.DesJarlais, C.Schubert, I.P.Petrounia, M.A.Chaikin, C.L.Manthey, M.R.Player.
 
  ABSTRACT  
 
A series of pyrimidinopyridones has been designed, synthesized and shown to be potent and selective inhibitors of the FMS tyrosine kinase. Introduction of an amide substituent at the 6-position of the pyridone core resulted in a significant potency increase. Compound 24 effectively inhibited in vivo LPS-induced TNF in mice greater than 80%.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21095574 L.M.Wodicka, P.Ciceri, M.I.Davis, J.P.Hunt, M.Floyd, S.Salerno, X.H.Hua, J.M.Ford, R.C.Armstrong, P.P.Zarrinkar, and D.K.Treiber (2010).
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
  Chem Biol, 17, 1241-1249.  
19590778 C.L.Gibson, J.K.Huggan, A.Kennedy, L.Kiefer, J.H.Lee, C.J.Suckling, C.Clements, A.L.Harvey, W.N.Hunter, and L.B.Tulloch (2009).
Diversity oriented syntheses of fused pyrimidines designed as potential antifolates.
  Org Biomol Chem, 7, 1829-1842.  
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.