spacer
spacer

PDBsum entry 2c4g

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Transferase PDB id
2c4g
Jmol
Contents
Protein chains
301 a.a. *
258 a.a. *
Ligands
SO4 ×2
514 ×2
Waters ×138
* Residue conservation analysis
PDB id:
2c4g
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)
Resolution:
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
Date:
19-Oct-05     Release date:   23-Nov-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 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   31 terms 
  Biochemical function     nucleotide binding     13 terms  

 

 
    reference    
 
 
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.
 
  ABSTRACT  
 
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).
4-[4-(Piperidin-1-yl)piperidin-1-yl]benzonitrile.
  Acta Crystallogr Sect E Struct Rep Online, 66, o284.  
20162627 O.Doppelt-Azeroual, F.Delfaud, F.Moriaud, and A.G.de 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.  
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.

 

spacer

spacer