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PDBsum entry 3e63

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protein ligands links
Transferase PDB id
3e63
Jmol PyMol
Contents
Protein chain
292 a.a. *
Ligands
5B2
Waters ×267
* Residue conservation analysis
PDB id:
3e63
Name: Transferase
Title: Fragment based discovery of jak-2 inhibitors
Structure: Tyrosine-protein kinase jak2. Chain: a. Fragment: catalytic domain (unp residues 839 to 1131). Synonym: janus kinase 2, jak-2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: jak2. Expressed in: unidentified baculovirus. Expression_system_taxid: 10469.
Resolution:
1.90Å     R-factor:   0.203     R-free:   0.263
Authors: S.Antonysamy,W.Fang,G.Hirst,F.Park,M.Russell,L.Smyth,P.Spren F.Stappenbeck,R.Steensma,D.A.Thompson,M.Wilson,M.Wong,A.Zha F.Zhang
Key ref: S.Antonysamy et al. (2009). Fragment-based discovery of JAK-2 inhibitors. Bioorg Med Chem Lett, 19, 279-282. PubMed id: 19019674
Date:
14-Aug-08     Release date:   14-Oct-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O60674  (JAK2_HUMAN) -  Tyrosine-protein kinase JAK2
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1132 a.a.
292 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.10.2  - Non-specific 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 = 5B2)
matches with 43.48% 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     2 terms  

 

 
    reference    
 
 
Bioorg Med Chem Lett 19:279-282 (2009)
PubMed id: 19019674  
 
 
Fragment-based discovery of JAK-2 inhibitors.
S.Antonysamy, G.Hirst, F.Park, P.Sprengeler, F.Stappenbeck, R.Steensma, M.Wilson, M.Wong.
 
  ABSTRACT  
 
Fragment-based hit identification coupled with crystallographically enabled structure-based drug design was used to design potent inhibitors of JAK-2. After two iterations from fragment 1, we were able to increase potency by greater than 500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20223699 A.G.Coyne, D.E.Scott, and C.Abell (2010).
Drugging challenging targets using fragment-based approaches.
  Curr Opin Chem Biol, 14, 299-307.  
20471246 C.W.Murray, and T.L.Blundell (2010).
Structural biology in fragment-based drug design.
  Curr Opin Struct Biol, 20, 497-507.  
20582381 T.Okuzumi, G.S.Ducker, C.Zhang, B.Aizenstein, R.Hoffman, and K.M.Shokat (2010).
Synthesis and evaluation of indazole based analog sensitive Akt inhibitors.
  Mol Biosyst, 6, 1389-1402.  
20191331 Y.Hitoshi, N.Lin, D.G.Payan, and V.Markovtsov (2010).
The current status and the future of JAK2 inhibitors for the treatment of myeloproliferative diseases.
  Int J Hematol, 91, 189-200.  
19447617 R.Kiss, T.Polgár, A.Kirabo, J.Sayyah, N.C.Figueroa, A.F.List, L.Sokol, K.S.Zuckerman, M.Gali, K.S.Bisht, P.P.Sayeski, and G.M.Keseru (2009).
Identification of a novel inhibitor of JAK2 tyrosine kinase by structure-based virtual screening.
  Bioorg Med Chem Lett, 19, 3598-3601.  
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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