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PDBsum entry 2b55

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protein ligands links
Transferase PDB id
2b55
Jmol
Contents
Protein chain
276 a.a. *
Ligands
D31
Waters ×104
* Residue conservation analysis
PDB id:
2b55
Name: Transferase
Title: Human cyclin dependent kinase 2 (cdk2) complexed with indenopyraxole din-101312
Structure: Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase, cdk2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Resolution:
1.85Å     R-factor:   0.213     R-free:   0.256
Authors: J.Muckelbauer
Key ref: E.W.Yue et al. (2002). Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. 3. Structure activity relationships at C3(1,2). J Med Chem, 45, 5233-5248. PubMed id: 12431051 DOI: 10.1021/jm0201722
Date:
27-Sep-05     Release date:   11-Oct-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
276 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: 10.1021/jm0201722 J Med Chem 45:5233-5248 (2002)
PubMed id: 12431051  
 
 
Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. 3. Structure activity relationships at C3(1,2).
E.W.Yue, C.A.Higley, S.V.DiMeo, D.J.Carini, D.A.Nugiel, C.Benware, P.A.Benfield, C.R.Burton, S.Cox, R.H.Grafstrom, D.M.Sharp, L.M.Sisk, J.F.Boylan, J.K.Muckelbauer, A.M.Smallwood, H.Chen, C.H.Chang, S.P.Seitz, G.L.Trainor.
 
  ABSTRACT  
 
The identification of indeno[1,2-c]pyrazol-4-ones as inhibitors of cyclin-dependent kinases (CDKs) has led to the discovery of a series of novel and potent compounds. Herein, we report the effects of substitutions at C3 of the indeno[1,2-c]pyrazol-4-one core with alkyls, heterocycles, and substituted phenyls. Substitutions at the para position of the phenyl ring at C3 were generally well-tolerated; however, larger groups were generally inactive. For alkyls directly attached to C3, longer chain substituents were not tolerated; however, shorter alkyl groups and cyclic alkyls were acceptable. In general, the heterocycles at C3 gave the most potent analogues. One such heterocycle, 24j, was examined in detail and was determined to have a biological profile consistent with CDK inhibition. An X-ray crystal structure of one of the alkyl compounds, 13q, complexed with CDK2 was determined and showed the inhibitor residing in the adenosine 5'-triphosphate pocket of the enzyme.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
15123283 F.Becker, K.Murthi, C.Smith, J.Come, N.Costa-Roldán, C.Kaufmann, U.Hanke, C.Degenhart, S.Baumann, W.Wallner, A.Huber, S.Dedier, S.Dill, D.Kinsman, M.Hediger, N.Bockovich, S.Meier-Ewert, A.F.Kluge, and N.Kley (2004).
A three-hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors.
  Chem Biol, 11, 211-223.  
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