PDBsum entry 2iw6

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protein ligands metals Protein-protein interface(s) links
Cell cycle PDB id
Protein chains
293 a.a. *
257 a.a. *
QQ2 ×2
SGM ×2
Waters ×114
* Residue conservation analysis
PDB id:
Name: Cell cycle
Title: Structure of human thr160-phospho cdk2-cyclin a complexed with a bisanilinopyrimidine inhibitor
Structure: Cell division protein kinase 2. Chain: a, c. Synonym: cyclin dependent kinase 2, p33 protein kinase. Engineered: yes. Mutation: yes. Other_details: phosphothreonine 160. Cyclin-a2. Chain: b, d. Fragment: a3, residues 174-432.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Other_details: wild type gene was a gift from dr d.O.Morgan other_details: full-length cyclin a was a gift from dr m.Do
Biol. unit: Tetramer (from PDB file)
2.30Å     R-factor:   0.231     R-free:   0.287
Authors: D.J.Pratt,J.Bentley,P.Jewsbury,F.T.Boyle,J.A.Endicott,M.E.M.
Key ref: D.J.Pratt et al. (2006). Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity. J Med Chem, 49, 5470-5477. PubMed id: 16942020 DOI: 10.1021/jm060216x
26-Jun-06     Release date:   06-Sep-06    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
298 a.a.
293 a.a.*
Protein chains
Pfam   ArchSchema ?
P20248  (CCNA2_HUMAN) -  Cyclin-A2
432 a.a.
257 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: Chains A, C: E.C.  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ 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   31 terms 
  Biochemical function     nucleotide binding     13 terms  


DOI no: 10.1021/jm060216x J Med Chem 49:5470-5477 (2006)
PubMed id: 16942020  
Dissecting the determinants of cyclin-dependent kinase 2 and cyclin-dependent kinase 4 inhibitor selectivity.
D.J.Pratt, J.Bentley, P.Jewsbury, F.T.Boyle, J.A.Endicott, M.E.Noble.
Cyclin dependent kinases are a key family of kinases involved in cell cycle regulation and are an attractive target for cancer chemotherapy. The roles of four residues of the cyclin-dependent kinase active site in inhibitor selectivity were investigated by producing cyclin-dependent kinase 2 mutants bearing equivalent cyclin-dependent kinase 4 residues, namely F82H, L83V, H84D, and K89T. Assay of the mutants with a cyclin-dependent kinase 4-selective bisanilinopyrimidine shows that the K89T mutation is primarily responsible for the selectivity of this compound. Use of the cyclin-dependent kinase 2-selective 6-cyclohexylmethoxy-2-(4'-sulfamoylanilino)purine (NU6102) shows that K89T has no role in the selectivity, while the remaining three mutations have a cumulative influence. The results indicate that certain residues that are not frequently considered in structure-aided kinase inhibitor design have an important role to play.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20575139 K.Engels, C.Beyer, M.L.Suárez Fernández, F.Bender, M.Gassel, G.Unden, R.J.Marhöfer, J.C.Mottram, and P.M.Selzer (2010).
Inhibition of Eimeria tenella CDK-related kinase 2: From target identification to lead compounds.
  ChemMedChem, 5, 1259-1271.  
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