PDBsum entry 3f9n

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protein ligands links
Transferase PDB id
Jmol PyMol
Protein chain
253 a.a. *
SO4 ×2
Waters ×257
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of chk1 kinase in complex with inhibitor 38
Structure: Serine/threonine-protein kinase chk1. Chain: a. Fragment: chk1 kinase domain: unp residues 2-307. Engineered: yes
Source: Homo sapiens. Organism_taxid: 9606. Gene: chek1, chk1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
1.90Å     R-factor:   0.184     R-free:   0.216
Authors: Y.Yan,S.Munshi,M.Ikuta
Key ref: A.Converso et al. (2009). Development of thioquinazolinones, allosteric Chk1 kinase inhibitors. Bioorg Med Chem Lett, 19, 1240-1244. PubMed id: 19155174
14-Nov-08     Release date:   20-Jan-09    
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Protein chain
Pfam   ArchSchema ?
O14757  (CHK1_HUMAN) -  Serine/threonine-protein kinase Chk1
476 a.a.
253 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ phosphoprotein
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  


Bioorg Med Chem Lett 19:1240-1244 (2009)
PubMed id: 19155174  
Development of thioquinazolinones, allosteric Chk1 kinase inhibitors.
A.Converso, T.Hartingh, R.M.Garbaccio, E.Tasber, K.Rickert, M.E.Fraley, Y.Yan, C.Kreatsoulas, S.Stirdivant, B.Drakas, E.S.Walsh, K.Hamilton, C.A.Buser, X.Mao, M.T.Abrams, S.C.Beck, W.Tao, R.Lobell, L.Sepp-Lorenzino, J.Zugay-Murphy, V.Sardana, S.K.Munshi, S.M.Jezequel-Sur, P.D.Zuck, G.D.Hartman.
A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at K(m) for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site approximately 13A from the ATP binding site. Preliminary data is presented for several of these compounds.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21087899 C.X.Ma, J.W.Janetka, and H.Piwnica-Worms (2011).
Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics.
  Trends Mol Med, 17, 88-96.  
21256157 R.Eglen, and T.Reisine (2011).
Drug discovery and the human kinome: recent trends.
  Pharmacol Ther, 130, 144-156.  
20072125 J.Zhang, F.J.Adrián, W.Jahnke, S.W.Cowan-Jacob, A.G.Li, R.E.Iacob, T.Sim, J.Powers, C.Dierks, F.Sun, G.R.Guo, Q.Ding, B.Okram, Y.Choi, A.Wojciechowski, X.Deng, G.Liu, G.Fendrich, A.Strauss, N.Vajpai, S.Grzesiek, T.Tuntland, Y.Liu, B.Bursulaya, M.Azam, P.W.Manley, J.R.Engen, G.Q.Daley, M.Warmuth, and N.S.Gray (2010).
Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors.
  Nature, 463, 501-506.
PDB code: 3k5v
20886116 W.I.Wu, W.C.Voegtli, H.L.Sturgis, F.P.Dizon, G.P.Vigers, and B.J.Brandhuber (2010).
Crystal structure of human AKT1 with an allosteric inhibitor reveals a new mode of kinase inhibition.
  PLoS One, 5, e12913.
PDB code: 3o96
19568781 L.A.Smyth, and I.Collins (2009).
Measuring and interpreting the selectivity of protein kinase inhibitors.
  J Chem Biol, 2, 131-151.  
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