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PDBsum entry 3lcd

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protein ligands links
Transferase PDB id
3lcd
Jmol
Contents
Protein chain
290 a.a. *
Ligands
SO4 ×2
BDY
Waters ×44
* Residue conservation analysis
PDB id:
3lcd
Name: Transferase
Title: Inhibitor bound to a dfg-in structure of the kinase domain o
Structure: Macrophage colony-stimulating factor 1 receptor. Chain: a. Fragment: kinase domain. Synonym: csf-1-r, fms proto-oncogene, c-fms. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: csf-1r, csf1r, fms. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.50Å     R-factor:   0.218     R-free:   0.265
Authors: S.Kamtekar,J.E.Day,B.A.Reitz,K.J.Mathis,M.J.Meyers
Key ref: M.J.Meyers et al. (2010). Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode. Bioorg Med Chem Lett, 20, 1543-1547. PubMed id: 20137931 DOI: 10.1016/j.bmcl.2010.01.078
Date:
10-Jan-10     Release date:   02-Mar-10    
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.
290 a.a.
Key:    PfamA domain  PfamB 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!
  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.2010.01.078 Bioorg Med Chem Lett 20:1543-1547 (2010)
PubMed id: 20137931  
 
 
Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode.
M.J.Meyers, M.Pelc, S.Kamtekar, J.Day, G.I.Poda, M.K.Hall, M.L.Michener, B.A.Reitz, K.J.Mathis, B.S.Pierce, M.D.Parikh, D.A.Mischke, S.A.Long, J.J.Parlow, D.R.Anderson, A.Thorarensen.
 
  ABSTRACT  
 
The work described herein demonstrates the utility of structure-based drug design (SBDD) in shifting the binding mode of an HTS hit from a DFG-in to a DFG-out binding mode resulting in a class of novel potent CSF-1R kinase inhibitors suitable for lead development.
 

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.  
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.