PDBsum entry 1pye

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Transferase PDB id
Protein chain
266 a.a. *
Waters ×130
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of cdk2 with inhibitor
Structure: Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
2.00Å     R-factor:   0.239     R-free:   0.252
Authors: F.Zhang,C.Hamdouchi
Key ref: C.Hamdouchi et al. (2004). The discovery of a new structural class of cyclin-dependent kinase inhibitors, aminoimidazo[1,2-a]pyridines. Mol Cancer Ther, 3, 1-9. PubMed id: 14749470 Ref: Full text
08-Jul-03     Release date:   13-Jul-04    
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Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
298 a.a.
266 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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  


Full text Mol Cancer Ther 3:1-9 (2004)
PubMed id: 14749470  
The discovery of a new structural class of cyclin-dependent kinase inhibitors, aminoimidazo[1,2-a]pyridines.
C.Hamdouchi, H.Keyser, E.Collins, C.Jaramillo, J.E.De Diego, C.D.Spencer, J.A.Dempsey, B.D.Anderson, T.Leggett, N.B.Stamm, R.M.Schultz, S.A.Watkins, K.Cocke, S.Lemke, T.F.Burke, R.P.Beckmann, J.T.Dixon, T.M.Gurganus, N.B.Rankl, K.A.Houck, F.Zhang, M.Vieth, J.Espinosa, D.E.Timm, R.M.Campbell, B.K.Patel, H.B.Brooks.
The protein kinase family represents an enormous opportunity for drug development. However, the current limitation in structural diversity of kinase inhibitors has complicated efforts to identify effective treatments of diseases that involve protein kinase signaling pathways. We have identified a new structural class of protein serine/threonine kinase inhibitors comprising an aminoimidazo[1,2-a]pyridine nucleus. In this report, we describe the first successful use of this class of aza-heterocycles to generate potent inhibitors of cyclin-dependent kinases that compete with ATP for binding to a catalytic subunit of the protein. Co-crystal structures of CDK2 in complex with lead compounds reveal a unique mode of binding. Using this knowledge, a structure-based design approach directed this chemical scaffold toward generating potent and selective CDK2 inhibitors, which selectively inhibited the CDK2-dependent phosphorylation of Rb and induced caspase-3-dependent apoptosis in HCT 116 tumor cells. The discovery of this new class of ATP-site-directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis for a new medicinal chemistry tool to be used in the search for effective treatments of cancer and other diseases that involve protein kinase signaling pathways.

Literature references that cite this PDB file's key reference

  PubMed id Reference
17492398 S.A.Choudhury, P.Kauler, S.Devic, and T.Y.Chow (2007).
Silencing of endo-exonuclease expression sensitizes mouse B16F10 melanoma cells to DNA damaging agents.
  Invest New Drugs, 25, 399-410.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
16264989 E.B.Haura, J.Turkson, and R.Jove (2005).
Mechanisms of disease: Insights into the emerging role of signal transducers and activators of transcription in cancer.
  Nat Clin Pract Oncol, 2, 315-324.  
16170026 N.T.Ihle, G.Paine-Murrieta, M.I.Berggren, A.Baker, W.R.Tate, P.Wipf, R.T.Abraham, D.L.Kirkpatrick, and G.Powis (2005).
The phosphatidylinositol-3-kinase inhibitor PX-866 overcomes resistance to the epidermal growth factor receptor inhibitor gefitinib in A-549 human non-small cell lung cancer xenografts.
  Mol Cancer Ther, 4, 1349-1357.  
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