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PDBsum entry 3du8
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protein ligands Protein-protein interface(s) links
Transferase PDB id
3du8

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
336 a.a. *
Ligands
553 ×2
Waters ×214
* Residue conservation analysis
PDB id:
3du8
Name: Transferase
Title: Crystal structure of gsk-3 beta in complex with nms-869553a
Structure: Glycogen synthase kinase-3 beta. Chain: a, b. Synonym: gsk-3 beta. Engineered: yes
Source: Homo sapiens. Organism_taxid: 9606. Gene: gsk3b. Expressed in: spodoptera frugiperda. Expression_system_cell_line: sf9.
Resolution:
2.20Å     R-factor:   0.215     R-free:   0.246
Authors: R.T.Bossi
Key ref: M.Menichincheri et al. (2009). First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery. J Med Chem, 52, 293-307. PubMed id: 19115845
Date:
17-Jul-08     Release date:   03-Mar-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P49841  (GSK3B_HUMAN) -  Glycogen synthase kinase-3 beta from Homo sapiens
Seq:
Struc: 		420 a.a.
336 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.26  - [tau protein] kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction:
1. L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H+
2. L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H+
L-seryl-[tau protein]
 + ATP
 = O-phospho-L-seryl-[tau protein]
 + ADP
 + H(+)
L-threonyl-[tau protein]
 + ATP
 = O-phospho-L-threonyl-[tau protein]
 + ADP
 + H(+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
J Med Chem 52:293-307 (2009)
PubMed id: 19115845  
 
 
First Cdc7 kinase inhibitors: pyrrolopyridinones as potent and orally active antitumor agents. 2. Lead discovery.
M.Menichincheri, A.Bargiotti, J.Berthelsen, J.A.Bertrand, R.Bossi, A.Ciavolella, A.Cirla, C.Cristiani, V.Croci, R.D'Alessio, M.Fasolini, F.Fiorentini, B.Forte, A.Isacchi, K.Martina, A.Molinari, A.Montagnoli, P.Orsini, F.Orzi, E.Pesenti, D.Pezzetta, A.Pillan, I.Poggesi, F.Roletto, A.Scolaro, M.Tatò, M.Tibolla, B.Valsasina, M.Varasi, D.Volpi, C.Santocanale, E.Vanotti.
 
  ABSTRACT  
 
Cdc7 kinase is a key regulator of the S-phase of the cell cycle, known to promote the activation of DNA replication origins in eukaryotic organisms. Cdc7 inhibition can cause tumor-cell death in a p53-independent manner, supporting the rationale for developing Cdc7 inhibitors for the treatment of cancer. In this paper, we conclude the structure-activity relationships study of the 2-heteroaryl-pyrrolopyridinone class of compounds that display potent inhibitory activity against Cdc7 kinase. Furthermore, we also describe the discovery of 89S, [(S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoro-ethyl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one], as a potent ATP mimetic inhibitor of Cdc7. Compound 89S has a Ki value of 0.5 nM, inhibits cell proliferation of different tumor cell lines with an IC50 in the submicromolar range, and exhibits in vivo tumor growth inhibition of 68% in the A2780 xenograft model.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21333571 C.Fang, Z.Xiao, and Z.Guo (2011).
Generation and validation of the first predictive pharmacophore model for cyclin-dependent kinase 9 inhibitors.
  J Mol Graph Model, 29, 800-808.  
  21469159 S.Y.Lu, Y.J.Jiang, J.Lv, J.W.Zou, and T.X.Wu (2011).
Role of bridging water molecules in GSK3β-inhibitor complexes: insights from QM/MM, MD, and molecular docking studies.
  J Comput Chem, 32, 1907-1918.  
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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