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PDBsum entry 1y8y

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Transferase PDB id
1y8y
Jmol
Contents
Protein chain
292 a.a. *
Ligands
CT7
Waters ×197
* Residue conservation analysis
PDB id:
1y8y
Name: Transferase
Title: Crystal structure of human cdk2 complexed with a pyrazolo[1, 5-a]pyrimidine 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.
Resolution:
2.00Å     R-factor:   0.194     R-free:   0.272
Authors: D.S.Williamson,M.J.Parratt,C.J.Torrance,J.F.Bower,J.D.Moore, C.M.Richardson,P.Dokurno,A.D.Cansfield,G.L.Francis, R.J.Hebdon,R.Howes,P.S.Jackson,A.M.Lockie,J.B.Murray, C.L.Nunns,J.Powles,A.Robertson,A.E.Surgenor
Key ref: D.S.Williamson et al. (2005). Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2. Bioorg Med Chem Lett, 15, 863-867. PubMed id: 15686876 DOI: 10.1016/j.bmcl.2004.12.073
Date:
14-Dec-04     Release date:   08-Feb-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
292 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
+ 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.2004.12.073 Bioorg Med Chem Lett 15:863-867 (2005)
PubMed id: 15686876  
 
 
Structure-guided design of pyrazolo[1,5-a]pyrimidines as inhibitors of human cyclin-dependent kinase 2.
D.S.Williamson, M.J.Parratt, J.F.Bower, J.D.Moore, C.M.Richardson, P.Dokurno, A.D.Cansfield, G.L.Francis, R.J.Hebdon, R.Howes, P.S.Jackson, A.M.Lockie, J.B.Murray, C.L.Nunns, J.Powles, A.Robertson, A.E.Surgenor, C.J.Torrance.
 
  ABSTRACT  
 
The protein structure guided design of a series of pyrazolo[1,5-a]pyrimidines with high potency for human cyclin-dependent kinase 2 (CDK2) is described. Some examples were shown to inhibit the growth of human colon tumour cells, were equipotent for CDK1 and were selective against GSK-3beta and other kinases.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19638587 S.Ali, D.A.Heathcote, S.H.Kroll, A.S.Jogalekar, B.Scheiper, H.Patel, J.Brackow, A.Siwicka, M.J.Fuchter, M.Periyasamy, R.S.Tolhurst, S.K.Kanneganti, J.P.Snyder, D.C.Liotta, E.O.Aboagye, A.G.Barrett, and R.C.Coombes (2009).
The development of a selective cyclin-dependent kinase inhibitor that shows antitumor activity.
  Cancer Res, 69, 6208-6215.  
18972468 C.Peifer, and D.R.Alessi (2008).
Small-molecule inhibitors of PDK1.
  ChemMedChem, 3, 1810-1838.  
17937404 T.O.Fischmann, A.Hruza, J.S.Duca, L.Ramanathan, T.Mayhood, W.T.Windsor, H.V.Le, T.J.Guzi, M.P.Dwyer, K.Paruch, R.J.Doll, E.Lees, D.Parry, W.Seghezzi, and V.Madison (2008).
Structure-guided discovery of cyclin-dependent kinase inhibitors.
  Biopolymers, 89, 372-379.
PDB codes: 2r3f 2r3g 2r3h 2r3i 2r3j 2r3k 2r3l 2r3m 2r3n 2r3o 2r3p 2r3q 2r3r
17571187 F.Marchetti, K.L.Sayle, J.Bentley, W.Clegg, N.J.Curtin, J.A.Endicott, B.T.Golding, R.J.Griffin, K.Haggerty, R.W.Harrington, V.Mesguiche, D.R.Newell, M.E.Noble, R.J.Parsons, D.J.Pratt, L.Z.Wang, and I.R.Hardcastle (2007).
Structure-based design of 2-arylamino-4-cyclohexylmethoxy-5-nitroso-6-aminopyrimidine inhibitors of cyclin-dependent kinase 2.
  Org Biomol Chem, 5, 1577-1585.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.