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PDBsum entry 1pye

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Transferase PDB id
1pye
Jmol
Contents
Protein chain
266 a.a. *
Ligands
PM1
Waters ×130
* Residue conservation analysis
PDB id:
1pye
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.
Resolution:
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
Date:
08-Jul-03     Release date:   13-Jul-04    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
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.
 
  ABSTRACT  
 
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.  
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.