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PDBsum entry 2v0d

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protein ligands metals links
Transferase PDB id
2v0d
Jmol
Contents
Protein chain
292 a.a. *
Ligands
C53
Metals
_CL
Waters ×219
* Residue conservation analysis
PDB id:
2v0d
Name: Transferase
Title: Crystal structure of human cdk2 complexed with a thiazolidinone inhibitor
Structure: Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase, cyclin dependent kinase 2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.20Å     R-factor:   0.197     R-free:   0.286
Authors: C.M.Richardson,P.Dokurno,J.B.Murray,A.E.Surgenor
Key ref: C.M.Richardson et al. (2007). Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping. Bioorg Med Chem Lett, 17, 3880-3885. PubMed id: 17570665 DOI: 10.1016/j.bmcl.2007.04.110
Date:
14-May-07     Release date:   26-Jun-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
292 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: 10.1016/j.bmcl.2007.04.110 Bioorg Med Chem Lett 17:3880-3885 (2007)
PubMed id: 17570665  
 
 
Discovery of a potent CDK2 inhibitor with a novel binding mode, using virtual screening and initial, structure-guided lead scoping.
C.M.Richardson, C.L.Nunns, D.S.Williamson, M.J.Parratt, P.Dokurno, R.Howes, J.Borgognoni, M.J.Drysdale, H.Finch, R.E.Hubbard, P.S.Jackson, P.Kierstan, G.Lentzen, J.D.Moore, J.B.Murray, H.Simmonite, A.E.Surgenor, C.J.Torrance.
 
  ABSTRACT  
 
Virtual screening against a pCDK2/cyclin A crystal structure led to the identification of a potent and novel CDK2 inhibitor, which exhibited an unusual mode of interaction with the kinase binding motif. With the aid of X-ray crystallography and modelling, a medicinal chemistry strategy was implemented to probe the interactions seen in the crystal structure and to establish SAR. A fragment-based approach was also considered but a different, more conventional, binding mode was observed. Compound selectivity against GSK-3beta was improved using a rational design strategy, with crystallographic verification of the CDK2 binding mode.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21360822 J.A.Pinson, O.Schmidt-Kittler, J.Zhu, I.G.Jennings, K.W.Kinzler, B.Vogelstein, D.K.Chalmers, and P.E.Thompson (2011).
Thiazolidinedione-Based PI3Kα Inhibitors: An Analysis of Biochemical and Virtual Screening Methods.
  ChemMedChem, 6, 514-522.  
20673774 R.E.Hubbard (2011).
Structure-based drug discovery and protein targets in the CNS.
  Neuropharmacology, 60, 7.  
20401681 N.Brooijmans, and C.Humblet (2010).
Chemical space sampling by different scoring functions and crystal structures.
  J Comput Aided Mol Des, 24, 433-447.  
21053053 N.Brooijmans, J.B.Cross, and C.Humblet (2010).
Biased retrieval of chemical series in receptor-based virtual screening.
  J Comput Aided Mol Des, 24, 1053-1062.  
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.