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PDBsum entry 2a0c

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protein ligands links
Transferase PDB id
2a0c
Jmol
Contents
Protein chain
294 a.a. *
Ligands
CK9
Waters ×134
* Residue conservation analysis
PDB id:
2a0c
Name: Transferase
Title: Human cdk2 in complex with olomoucine ii, a novel 2,6,9- trisubstituted purine cyclin-dependent kinase inhibitor
Structure: Cell division protein kinase 2. Chain: x. Synonym: cyclin dependant kinase 2, cdk2, p33 protein kinase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2.
Resolution:
1.95Å     R-factor:   0.194     R-free:   0.244
Authors: V.Krystof,I.W.Mcnae,M.D.Walkinshaw,P.M.Fischer,P.Muller, B.Vojtesek,M.Orsag,L.Havlicek,M.Strnad
Key ref: V.Krystof et al. (2005). Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor. Cell Mol Life Sci, 62, 1763-1771. PubMed id: 16003486 DOI: 10.1007/s00018-005-5185-1
Date:
16-Jun-05     Release date:   24-Jan-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
294 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.7.11.22  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
ATP
+ protein
=
ADP
Bound ligand (Het Group name = CK9)
matches with 42.00% similarity
+ phosphoprotein
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cyclin-dependent protein kinase holoenzyme complex   15 terms 
  Biological process     regulation of gene silencing   27 terms 
  Biochemical function     nucleotide binding     12 terms  

 

 
    reference    
 
 
DOI no: 10.1007/s00018-005-5185-1 Cell Mol Life Sci 62:1763-1771 (2005)
PubMed id: 16003486  
 
 
Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor.
V.Krystof, I.W.McNae, M.D.Walkinshaw, P.M.Fischer, P.Müller, B.Vojtesek, M.Orság, L.Havlícek, M.Strnad.
 
  ABSTRACT  
 
The study describes the protein kinase selectivity profile, as well as the binding mode of olomoucine II in the catalytic cleft of CDK2, as determined from cocrystal analysis. Apart from the main cell cycle-regulating kinase CDK2, olomoucine II exerts specificity for CDK7 and CDK9, with important functions in the regulation of RNA transcription. In vitro anticancer activity of the inhibitor in a panel of tumor cell lines shows a wide potency range with a slight preference for cells harboring a wild-type p53 gene. Cell-based assays confirmed activation of p53 protein levels and events leading to accumulation of p21(WAF1). Additionally, in olomoucine II-treated cells, Mdm2 was found to form a complex with the ribosomal protein L11, which inhibits Mdm2 ubiquitin ligase function. We conclude that perturbations in RNA synthesis may lead to activation of p53 and that this contributes to the antiproliferative potency of cyclindependent kinase inhibitors.
 

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.  
20960514 Z.Holubcová, P.Matula, M.Sedláčková, V.Vinarský, D.Doležalová, T.Bárta, P.Dvořák, and A.Hampl (2011).
Human embryonic stem cells suffer from centrosomal amplification.
  Stem Cells, 29, 46-56.  
  20054100 J.Holcakova, P.Tomasec, J.J.Bugert, E.C.Wang, G.W.Wilkinson, R.Hrstka, V.Krystof, M.Strnad, and B.Vojtesek (2010).
The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent antiviral properties.
  Antivir Chem Chemother, 20, 133-142.  
19737069 Z.Koledova, L.R.Kafkova, L.Calabkova, V.Krystof, P.Dolezel, and V.Divoky (2010).
Cdk2 inhibition prolongs G1 phase progression in mouse embryonic stem cells.
  Stem Cells Dev, 19, 181-194.  
19723060 J.Wesierska-Gadek, and V.Krystof (2009).
Selective cyclin-dependent kinase inhibitors discriminating between cell cycle and transcriptional kinases: future reality or utopia?
  Ann N Y Acad Sci, 1171, 228-241.  
19308936 M.Paprskárová, V.Krystof, R.Jorda, P.Dzubák, M.Hajdúch, J.Wesierska-Gadek, and M.Strnad (2009).
Functional p53 in cells contributes to the anticancer effect of the cyclin-dependent kinase inhibitor roscovitine.
  J Cell Biochem, 107, 428-437.  
21581908 M.Rouchal, M.Nečas, F.P.de Carvalho, and R.Vícha (2009).
2-(1-Adamant-yl)-1-{4-[(2-chloro-9-isopropyl-9H-purin-6-yl)amino-meth-yl]phen-yl}ethanone.
  Acta Crystallogr Sect E Struct Rep Online, 65, o298-o299.  
17182854 T.N.Feinstein, and A.D.Linstedt (2007).
Mitogen-activated protein kinase kinase 1-dependent Golgi unlinking occurs in G2 phase and promotes the G2/M cell cycle transition.
  Mol Biol Cell, 18, 594-604.  
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.