PDBsum entry 2c4g

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protein ligands Protein-protein interface(s) links
Transferase PDB id
Protein chains
301 a.a. *
258 a.a. *
SO4 ×2
514 ×2
Waters ×138
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Structure of cdk2-cyclin a with pha-533514
Structure: Cell division protein kinase 2. Chain: a, c. Synonym: p33 protein kinase. Engineered: yes. Cyclin a2. Chain: b, d. Fragment: residues 173-432 (c-terminal portion). Synonym: cyclin a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: trichoplusia ni. Expression_system_taxid: 7111. Expression_system_cell_line: highfive. Expressed in: escherichia coli. Expression_system_taxid: 511693.
Biol. unit: Dimer (from PDB file)
2.7Å     R-factor:   0.233     R-free:   0.250
Authors: A.Cameron,G.Fogliatto,P.Pevarello,D.Fancelli,A.Vulpetti, R.Amici,M.Villa,V.Pittala,M.Ciomei,C.Mercurio,J.R.Bischoff, F.Roletto,M.Varasi,M.G.Brasca
Key ref: P.Pevarello et al. (2006). 3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: a new class of CDK2 inhibitors. Bioorg Med Chem Lett, 16, 1084-1090. PubMed id: 16290148 DOI: 10.1016/j.bmcl.2005.10.071
19-Oct-05     Release date:   23-Nov-05    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
298 a.a.
301 a.a.
Protein chains
Pfam   ArchSchema ?
P20248  (CCNA2_HUMAN) -  Cyclin-A2
432 a.a.
258 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 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: 10.1016/j.bmcl.2005.10.071 Bioorg Med Chem Lett 16:1084-1090 (2006)
PubMed id: 16290148  
3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: a new class of CDK2 inhibitors.
P.Pevarello, D.Fancelli, A.Vulpetti, R.Amici, M.Villa, V.Pittalà, P.Vianello, A.Cameron, M.Ciomei, C.Mercurio, J.R.Bischoff, F.Roletto, M.Varasi, M.G.Brasca.
We have recently reported about a new class of Aurora-A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. Here we describe the synthesis and early expansion of CDK2/cyclin A-E inhibitors belonging to the same chemical class. Synthesis of the compounds was accomplished using a solution-phase protocol amenable to rapid parallel expansion. Compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit CDK2-mediated tumor cell proliferation have been obtained.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21579720 G.B.Xu, J.Y.Shi, L.J.Chen, and Y.F.Luo (2010).
  Acta Crystallogr Sect E Struct Rep Online, 66, o284.  
20162627 O.Doppelt-Azeroual, F.Delfaud, F.Moriaud, and Brevern (2010).
Fast and automated functional classification with MED-SuMo: an application on purine-binding proteins.
  Protein Sci, 19, 847-867.  
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.  
17450625 M.G.Brasca, C.Albanese, R.Amici, D.Ballinari, L.Corti, V.Croci, D.Fancelli, F.Fiorentini, M.Nesi, P.Orsini, F.Orzi, W.Pastori, E.Perrone, E.Pesenti, P.Pevarello, F.Riccardi-Sirtori, F.Roletto, P.Roussel, M.Varasi, A.Vulpetti, and C.Mercurio (2007).
6-Substituted Pyrrolo[3,4-c]pyrazoles: An Improved Class of CDK2 Inhibitors.
  ChemMedChem, 2, 841-852.  
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