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PDBsum entry 4nj3

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protein ligands links
Transferase/transferase inhibitor PDB id
4nj3
Jmol
Contents
Protein chain
282 a.a.
Ligands
2KD
Waters ×161
PDB id:
4nj3
Name: Transferase/transferase inhibitor
Title: Modulating the interaction between cdk2 and cyclin a with a based inhibitor
Structure: Cyclin-dependent kinase 2. Chain: a. Fragment: cdk2. Synonym: cell division protein kinase 2, p33 protein kinase engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2, cdkn2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9
Resolution:
1.85Å     R-factor:   0.184     R-free:   0.231
Authors: T.O.Fischmann,A.W.Hruza
Key ref: Y.Deng et al. (2014). Modulating the interaction between CDK2 and cyclin A with a quinoline-based inhibitor. Bioorg Med Chem Lett, 24, 199-203. PubMed id: 24332088 DOI: 10.1016/j.bmcl.2013.11.041
Date:
08-Nov-13     Release date:   27-Nov-13    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
281 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 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
+ 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: 10.1016/j.bmcl.2013.11.041 Bioorg Med Chem Lett 24:199-203 (2014)
PubMed id: 24332088  
 
 
Modulating the interaction between CDK2 and cyclin A with a quinoline-based inhibitor.
Y.Deng, G.W.Shipps, L.Zhao, M.A.Siddiqui, J.Popovici-Muller, P.J.Curran, J.S.Duca, A.W.Hruza, T.O.Fischmann, V.S.Madison, R.Zhang, C.W.McNemar, T.W.Mayhood, R.Syto, A.Annis, P.Kirschmeier, E.M.Lees, D.A.Parry, W.T.Windsor.
 
  ABSTRACT  
 
A new class of quinoline-based kinase inhibitors has been discovered that both disrupt cyclin dependent 2 (CDK2) interaction with its cyclin A subunit and act as ATP competitive inhibitors. The key strategy for discovering this class of protein-protein disrupter compounds was to screen the monomer CDK2 in an affinity-selection/mass spectrometry-based technique and to perform secondary assays that identified compounds that bound only to the inactive CDK2 monomer and not the active CDK2/cyclin A heterodimer. Through a series of chemical modifications the affinity (Kd) of the original hit improved from 1 to 0.005μM.