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PDBsum entry 3js2

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protein ligands Protein-protein interface(s) links
Transferase PDB id
3js2
Jmol PyMol
Contents
Protein chains
295 a.a. *
Ligands
VM1 ×2
PO4 ×2
Waters ×142
* Residue conservation analysis
PDB id:
3js2
Name: Transferase
Title: Crystal structure of minimal kinase domain of fibroblast growth factor receptor 1 in complex with 5-(2-thienyl) nicotinic acid
Structure: Basic fibroblast growth factor receptor 1. Chain: a, b. Fragment: kinase domain: unp residues 459-765. Synonym: fgfr-1, bfgf-r, fms-like tyrosine kinase 2, c-fgr. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: fgfr1, fgfbr, flg, flt2. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.20Å     R-factor:   0.216     R-free:   0.259
Authors: J.H.Bae,K.P.Ravindranathan,V.Mandiyan,A.R.Ekkati, J.Schlessinger,W.L.Jorgensen
Key ref: K.P.Ravindranathan et al. (2010). Discovery of novel fibroblast growth factor receptor 1 kinase inhibitors by structure-based virtual screening. J Med Chem, 53, 1662-1672. PubMed id: 20121196
Date:
09-Sep-09     Release date:   23-Feb-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P11362  (FGFR1_HUMAN) -  Fibroblast growth factor receptor 1
Seq:
Struc:
 
Seq:
Struc:
822 a.a.
295 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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
Bound ligand (Het Group name = VM1)
matches with 47.00% similarity
= 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     protein kinase activity     3 terms  

 

 
    reference    
 
 
J Med Chem 53:1662-1672 (2010)
PubMed id: 20121196  
 
 
Discovery of novel fibroblast growth factor receptor 1 kinase inhibitors by structure-based virtual screening.
K.P.Ravindranathan, V.Mandiyan, A.R.Ekkati, J.H.Bae, J.Schlessinger, W.L.Jorgensen.
 
  ABSTRACT  
 
Fibroblast growth factors (FGFs) play important roles in embryonic development, angiogenesis, wound healing, and cell proliferation and differentiation. In search of inhibitors of FGFR1 kinase, 2.2 million compounds were docked into the ATP binding site of the protein. A co-crystal structure, which shows two alternative conformations for the nucleotide binding loop, is reported. Docking was performed on both conformations and, ultimately, 23 diverse compounds were purchased and assayed. Following hit validation, two compounds 10 and 16, a benzylidene derivative of pseudothiohydantoin and a thienopyrimidinone derivative, respectively, were discovered that inhibit FGFR1 kinase with IC(50) values of 23 and 50 microM. Initial optimization of 16 led to the more unsaturated 40, which has significantly enhanced potency, 1.9 microM. The core structures represent new structural motifs for FGFR1 kinase inhibitors. The study also illustrates complexities associated with the choice of protein structures for docking, possible use of multiple kinase structures to seek selectivity, and hit identification.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21516197 A.R.Ekkati, V.Madiyan, K.P.Ravindranathan, J.H Bae, J.Schlessinger, and W.L.Jorgensen (2011).
Aryl Extensions of Thienopyrimidinones as Fibroblast Growth Factor Receptor 1 Kinase Inhibitors.
  Tetrahedron Lett, 52, 2228-2231.  
21387347 B.Collignon, R.Schulz, J.C.Smith, and J.Baudry (2011).
Task-parallel message passing interface implementation of Autodock4 for docking of very large databases of compounds using high-performance super-computers.
  J Comput Chem, 32, 1202-1209.  
21373680 W.B.Wu, S.H.Chen, J.Q.Hou, J.H.Tan, T.M.Ou, S.L.Huang, D.Li, L.Q.Gu, and Z.S.Huang (2011).
Disubstituted 2-phenyl-benzopyranopyrimidine derivatives as a new type of highly selective ligands for telomeric G-quadruplex DNA.
  Org Biomol Chem, 9, 2975-2986.  
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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