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PDBsum entry 1jvp

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protein ligands links
Transferase PDB id
1jvp
Jmol
Contents
Protein chain
281 a.a. *
Ligands
LIG
Waters ×264
* Residue conservation analysis
PDB id:
1jvp
Name: Transferase
Title: Crystal structure of human cdk2 (unphosphorylated) in complex with pkf049-365
Structure: Cell division protein kinase 2. Chain: p. Synonym: p33 protein kinase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: h5 (trichoplusia ni).
Resolution:
1.53Å     R-factor:   0.206     R-free:   0.253
Authors: J.M.Rondeau
Key ref: P.Furet et al. (2002). Structure-based design and protein X-ray analysis of a protein kinase inhibitor. Bioorg Med Chem Lett, 12, 221-224. PubMed id: 11755359 DOI: 10.1016/S0960-894X(01)00715-6
Date:
31-Aug-01     Release date:   21-Dec-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
281 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/S0960-894X(01)00715-6 Bioorg Med Chem Lett 12:221-224 (2002)
PubMed id: 11755359  
 
 
Structure-based design and protein X-ray analysis of a protein kinase inhibitor.
P.Furet, T.Meyer, A.Strauss, S.Raccuglia, J.M.Rondeau.
 
  ABSTRACT  
 
A 5-aryl-1H-pyrazole molecular scaffold was designed to ligate the ATP binding site of cyclin dependent kinase 2 (CDK2) on the basis of crystallographic information. A search of the compound collection of Novartis using this scaffold as substructure query led to the identification of PKF049-365 as a representative of a new class of inhibitors of the cell cycle kinases CDK1/2. The three-dimensional structure of CDK2 in complex with PKF049-365 was subsequently determined by protein crystallography and refined to 1.53 A resolution. The X-ray analysis confirmed the binding mode expected from the design hypothesis. In addition, it revealed an alternative binding orientation involving a second tautomeric form of the inhibitor that was not envisaged during the design stage.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21053051 A.K.Malde, and A.E.Mark (2011).
Challenges in the determination of the binding modes of non-standard ligands in X-ray crystal complexes.
  J Comput Aided Mol Des, 25, 1.  
20354892 J.R.Greenwood, D.Calkins, A.P.Sullivan, and J.C.Shelley (2010).
Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution.
  J Comput Aided Mol Des, 24, 591-604.  
19368882 D.L.Mobley, and K.A.Dill (2009).
Binding of small-molecule ligands to proteins: "what you see" is not always "what you get".
  Structure, 17, 489-498.  
17294247 I.Schellhammer, and M.Rarey (2007).
TrixX: structure-based molecule indexing for large-scale virtual screening in sublinear time.
  J Comput Aided Mol Des, 21, 223-238.  
18043801 T.Persson, C.W.Yde, J.E.Rasmussen, T.L.Rasmussen, B.Guerra, O.G.Issinger, and J.Nielsen (2007).
Pyrazole carboxamides and carboxylic acids as protein kinase inhibitors in aberrant eukaryotic signal transduction: induction of growth arrest in MCF-7 cancer cells.
  Org Biomol Chem, 5, 3963-3970.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
12237154 M.Knockaert, P.Greengard, and L.Meijer (2002).
Pharmacological inhibitors of cyclin-dependent kinases.
  Trends Pharmacol Sci, 23, 417-425.  
12133723 P.L.Toogood (2002).
Progress toward the development of agents to modulate the cell cycle.
  Curr Opin Chem Biol, 6, 472-478.  
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.