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PDBsum entry 2qhm
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protein ligands links
Transferase PDB id
2qhm

 

 

 

 

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JSmol PyMol  
Contents
Protein chain
268 a.a. *
Ligands
7CS
Waters ×207
* Residue conservation analysis
PDB id:
2qhm
Name: Transferase
Title: Crystal structure of chek1 in complex with inhibitor 2a
Structure: Serine/threonine-protein kinase chk1. Chain: a. Fragment: protein kinase domain, residues 1-307. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.00Å     R-factor:   0.195     R-free:   0.237
Authors: Y.Yan,S.Munshi
Key ref: E.J.Brnardic et al. (2007). Optimization of a pyrazoloquinolinone class of Chk1 kinase inhibitors. Bioorg Med Chem Lett, 17, 5989-5994. PubMed id: 17804227
Date:
02-Jul-07     Release date:   18-Mar-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O14757  (CHK1_HUMAN) -  Serine/threonine-protein kinase Chk1 from Homo sapiens
Seq:
Struc: 		476 a.a.
268 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:
1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H+
L-seryl-[protein]
 + ATP
 = O-phospho-L-seryl-[protein]
 + ADP
 + H(+)
L-threonyl-[protein]
 + ATP
 = O-phospho-L-threonyl-[protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
Bioorg Med Chem Lett 17:5989-5994 (2007)
PubMed id: 17804227  
 
 
Optimization of a pyrazoloquinolinone class of Chk1 kinase inhibitors.
E.J.Brnardic, R.M.Garbaccio, M.E.Fraley, E.S.Tasber, J.T.Steen, K.L.Arrington, V.Y.Dudkin, 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 2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-ones as inhibitors of Chk1 kinase is described. Introduction of a fused ring at the C7/C8 positions of the pyrazoloquinolinone provided an increase in potency while guidance from overlapping inhibitor bound Chk1 X-ray crystal structures contributed to the discovery of a potent and solubilizing propyl amine moiety in compound 52 (Chk1 IC(50)=3.1 nM).
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20020310 X.M.Chen, T.Lu, S.Lu, H.F.Li, H.L.Yuan, T.Ran, H.C.Liu, and Y.D.Chen (2010).
Structure-based and shape-complemented pharmacophore modeling for the discovery of novel checkpoint kinase 1 inhibitors.
  J Mol Model, 16, 1195-1204.  
19220318 A.G.Villaseñor, R.Kondru, H.Ho, S.Wang, E.Papp, D.Shaw, J.W.Barnett, M.F.Browner, and A.Kuglstatter (2009).
Structural insights for design of potent spleen tyrosine kinase inhibitors from crystallographic analysis of three inhibitor complexes.
  Chem Biol Drug Des, 73, 466-470.
PDB codes: 3fqe 3fqh 3fqs
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.

 

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