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PDBsum entry 2g9x

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protein ligands Protein-protein interface(s) links
Transferase/cell cycle PDB id
2g9x
Jmol
Contents
Protein chains
299 a.a. *
262 a.a. *
275 a.a. *
Ligands
NU5 ×2
Waters ×161
* Residue conservation analysis
PDB id:
2g9x
Name: Transferase/cell cycle
Title: Structure of thr 160 phosphorylated cdk2/cyclin a in complex inhibitor nu6271
Structure: Cell division protein kinase 2. Chain: a, c. Synonym: p33 protein kinase. Engineered: yes. Cyclin-a2. Chain: b, d. Synonym: cyclin-a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: escherichia coli. Expression_system_taxid: 562. Bos taurus. Cattle. Organism_taxid: 9913.
Biol. unit: Dimer (from PQS)
Resolution:
2.50Å     R-factor:   0.219     R-free:   0.265
Authors: A.Echalier,J.A.Endicott,M.E.Noble
Key ref: R.J.Griffin et al. (2006). Searching for cyclin-dependent kinase inhibitors using a new variant of the cope elimination. J Am Chem Soc, 128, 6012-6013. PubMed id: 16669651 DOI: 10.1021/ja060595j
Date:
07-Mar-06     Release date:   23-May-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
299 a.a.*
Protein chains
Pfam   ArchSchema ?
P30274  (CCNA2_BOVIN) -  Cyclin-A2
Seq:
Struc:
430 a.a.
262 a.a.*
Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
275 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, C: 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   30 terms 
  Biochemical function     nucleotide binding     13 terms  

 

 
    reference    
 
 
DOI no: 10.1021/ja060595j J Am Chem Soc 128:6012-6013 (2006)
PubMed id: 16669651  
 
 
Searching for cyclin-dependent kinase inhibitors using a new variant of the cope elimination.
R.J.Griffin, A.Henderson, N.J.Curtin, A.Echalier, J.A.Endicott, I.R.Hardcastle, D.R.Newell, M.E.Noble, L.Z.Wang, B.T.Golding.
 
  ABSTRACT  
 
beta-Piperidinoethylsulfides are oxidized by m-chloroperbenzoic acid to intermediates containing both N-oxide and sulfone functions. These undergo a Cope-type elimination to a vinylsulfone that can be captured by amines to afford beta-aminoethylsulfones. When a beta-aminoethylsulfone group is linked to the 4-position of a phenyl group attached at N-2 of O6-cyclohexylmethylguanine, the resulting derivatives are inhibitors of the cyclin-dependent kinase CDK2. One of the most potent inhibitors (IC50 = 45 nM) contained a N-3-hydroxypropyl group on the aminoethylsulfonyl substituent. The crystal structure of this inhibitor bound to CDK2/cyclin A was determined and shows an unusual network of hydrogen bonds. The synthetic methodology developed can be utilized in multiple-parallel format and has numerous potential applications in medicinal chemistry.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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