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PDBsum entry 2hog

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protein ligands links
Transferase PDB id
2hog
Jmol PyMol
Contents
Protein chain
272 a.a. *
Ligands
710
Waters ×232
* Residue conservation analysis
PDB id:
2hog
Name: Transferase
Title: Crystal structure of chek1 in complex with inhibitor 20
Structure: Serine/threonine-protein kinase chk1. Chain: a. Fragment: kinase domain, residues 2-307. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: chek1, chk1. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
1.90Å     R-factor:   0.204     R-free:   0.236
Authors: Y.Yan,M.Ikuta
Key ref: M.E.Fraley et al. (2006). 3-(Indol-2-yl)indazoles as Chek1 kinase inhibitors: Optimization of potency and selectivity via substitution at C6. Bioorg Med Chem Lett, 16, 6049-6053. PubMed id: 16978863
Date:
14-Jul-06     Release date:   24-Apr-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O14757  (CHK1_HUMAN) -  Serine/threonine-protein kinase Chk1
Seq:
Struc:
476 a.a.
272 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.1  - Non-specific serine/threonine protein kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
= ADP
+ 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  

 

 
    reference    
 
 
Bioorg Med Chem Lett 16:6049-6053 (2006)
PubMed id: 16978863  
 
 
3-(Indol-2-yl)indazoles as Chek1 kinase inhibitors: Optimization of potency and selectivity via substitution at C6.
M.E.Fraley, J.T.Steen, E.J.Brnardic, K.L.Arrington, K.L.Spencer, B.A.Hanney, Y.Kim, G.D.Hartman, S.M.Stirdivant, B.A.Drakas, K.Rickert, E.S.Walsh, K.Hamilton, C.A.Buser, J.Hardwick, W.Tao, S.C.Beck, X.Mao, R.B.Lobell, L.Sepp-Lorenzino, Y.Yan, M.Ikuta, S.K.Munshi, L.C.Kuo, C.Kreatsoulas.
 
  ABSTRACT  
 
The development of 3-(indol-2-yl)indazoles as inhibitors of Chek1 kinase is described. Introduction of amides and heteroaryl groups at the C6 position of the indazole ring system provided sufficient Chek1 potency and selectivity over Cdk7 to permit escape from DNA damage-induced arrest in a cellular assay. Enzyme potency against Chek1 was optimized by the incorporation of a hydroxymethyl triazole moiety in compound 21 (Chek1 IC(50)=0.30nM) that was shown by X-ray crystallography to displace one of three highly conserved water molecules in the HI region of the ATP-binding cleft.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20689981 S.Qian, J.Cao, Y.Yan, M.Sun, H.Zhu, Y.Hu, Q.He, and B.Yang (2010).
SMT-A07, a 3-(Indol-2-yl) indazole derivative, induces apoptosis of leukemia cells in vitro.
  Mol Cell Biochem, 345, 13-21.  
17854022 K.L.Arrington, and V.Y.Dudkin (2007).
Novel Inhibitors of Checkpoint Kinase 1.
  ChemMedChem, 2, 1571-1585.  
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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