spacer
spacer

PDBsum entry 2uzo

Go to PDB code: 
protein ligands links
Transferase PDB id
2uzo
Jmol PyMol
Contents
Protein chain
290 a.a. *
Ligands
C62
Waters ×71
* Residue conservation analysis
PDB id:
2uzo
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:
2.30Å     R-factor:   0.215     R-free:   0.291
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:
30-Apr-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.
290 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 A1-CDK2 complex   19 terms 
  Biological process     regulation of gene silencing   32 terms 
  Biochemical function     nucleotide binding     13 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.

 

spacer

spacer