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PDBsum entry 1urw

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protein ligands links
Transferase PDB id
1urw
Jmol
Contents
Protein chain
275 a.a. *
Ligands
I1P
Waters ×210
* Residue conservation analysis
PDB id:
1urw
Name: Transferase
Title: Cdk2 in complex with an imidazo[1,2-b]pyridazine
Structure: Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase. Engineered: yes. Other_details: n-terminal methionine is modified by acetylation
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
1.6Å     R-factor:   0.220     R-free:   0.253
Authors: K.F.Byth,N.Cooper,J.D.Culshaw,D.W.Heaton,S.E.Oakes, C.A.Minshull,R.A.Norman,R.A.Pauptit,J.A.Tucker,J.Breed, A.Pannifer,S.Rowsell,J.J.Stanway,A.L.Valentine,A.P.Thomas
Key ref: K.F.Byth et al. (2004). Imidazo[1,2-b]pyridazines: a potent and selective class of cyclin-dependent kinase inhibitors. Bioorg Med Chem Lett, 14, 2249-2252. PubMed id: 15081018 DOI: 10.1016/j.bmcl.2004.02.008
Date:
11-Nov-03     Release date:   23-Apr-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
274 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.2004.02.008 Bioorg Med Chem Lett 14:2249-2252 (2004)
PubMed id: 15081018  
 
 
Imidazo[1,2-b]pyridazines: a potent and selective class of cyclin-dependent kinase inhibitors.
K.F.Byth, N.Cooper, J.D.Culshaw, D.W.Heaton, S.E.Oakes, C.A.Minshull, R.A.Norman, R.A.Pauptit, J.A.Tucker, J.Breed, A.Pannifer, S.Rowsell, J.J.Stanway, A.L.Valentine, A.P.Thomas.
 
  ABSTRACT  
 
Modification of imidazo[1,2-a]pyridine CDK inhibitors lead to identification of less lipophilic imidazo[1,2-b]pyridazine series of CDK inhibitors. Although several equivalent compounds from these two series have similar structure and show similar CDK activity, the SAR of the two series differs significantly. Protein inhibitor structure determination has confirmed differences in binding mode and given some understanding of these differences in SAR. Potent and selective imidazo[1,2-b]pyridazine inhibitors of CDK2 have been identified, which show >1 microM plasma levels following a 2mg/kg oral dose to mice.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19194508 J.Xiang, H.Yang, C.Che, H.Zou, H.Yang, Y.Wei, J.Quan, H.Zhang, Z.Yang, and S.Lin (2009).
Identifying tumor cell growth inhibitors by combinatorial chemistry and zebrafish assays.
  PLoS ONE, 4, e4361.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
16218947 A.K.Dunker, M.S.Cortese, P.Romero, L.M.Iakoucheva, and V.N.Uversky (2005).
Flexible nets. The roles of intrinsic disorder in protein interaction networks.
  FEBS J, 272, 5129-5148.  
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.