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PDBsum entry 1h00

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protein ligands links
Transferase PDB id
1h00
Jmol
Contents
Protein chain
279 a.a. *
Ligands
FAP
FCP
Waters ×209
* Residue conservation analysis
PDB id:
1h00
Name: Transferase
Title: Cdk2 in complex with a disubstituted 4, 6-bis anilino pyrimidine cdk4 inhibitor
Structure: Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
1.60Å     R-factor:   0.208     R-free:   0.242
Authors: J.F.Beattie,G.A.Breault,R.P.A.Ellston,S.Green,P.J.Jewsbury, C.J.Midgley,R.T.Naven,C.A.Minshull,R.A.Pauptit,J.A.Tucker, J.E.Pease
Key ref: J.F.Beattie et al. (2003). Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 1: identification and optimisation of substituted 4,6-bis anilino pyrimidines. Bioorg Med Chem Lett, 13, 2955-2960. PubMed id: 12941311 DOI: 10.1016/S0960-894X(03)00202-6
Date:
10-Jun-02     Release date:   11-Jul-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
278 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(03)00202-6 Bioorg Med Chem Lett 13:2955-2960 (2003)
PubMed id: 12941311  
 
 
Cyclin-dependent kinase 4 inhibitors as a treatment for cancer. Part 1: identification and optimisation of substituted 4,6-bis anilino pyrimidines.
J.F.Beattie, G.A.Breault, R.P.Ellston, S.Green, P.J.Jewsbury, C.J.Midgley, R.T.Naven, C.A.Minshull, R.A.Pauptit, J.A.Tucker, J.E.Pease.
 
  ABSTRACT  
 
Using a high-throughput screening campaign, we identified the 4,6-bis anilino pyrimidines as inhibitors of the cyclin-dependent kinase, CDK4. Herein we describe the further chemical modification and use of X-ray crystallography to develop potent and selective in vitro inhibitors of CDK4.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20828158 X.Deng, B.Okram, Q.Ding, J.Zhang, Y.Choi, F.J.Adrián, A.Wojciechowski, G.Zhang, J.Che, B.Bursulaya, S.W.Cowan-Jacob, G.Rummel, T.Sim, and N.S.Gray (2010).
Expanding the diversity of allosteric bcr-abl inhibitors.
  J Med Chem, 53, 6934-6946.  
19030106 D.Lietha, and M.J.Eck (2008).
Crystal structures of the FAK kinase in complex with TAE226 and related bis-anilino pyrimidine inhibitors reveal a helical DFG conformation.
  PLoS ONE, 3, e3800.
PDB codes: 2jkk 2jkm 2jko 2jkq
16374623 A.T.García-Sosa, and R.L.Mancera (2006).
The effect of a tightly bound water molecule on scaffold diversity in the computer-aided de novo ligand design of CDK2 inhibitors.
  J Mol Model, 12, 422-431.  
17205374 G.A.Landrum, J.E.Penzotti, and S.Putta (2006).
Feature-map vectors: a new class of informative descriptors for computational drug discovery.
  J Comput Aided Mol Des, 20, 751-762.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
15772071 R.I.Feldman, J.M.Wu, M.A.Polokoff, M.J.Kochanny, H.Dinter, D.Zhu, S.L.Biroc, B.Alicke, J.Bryant, S.Yuan, B.O.Buckman, D.Lentz, M.Ferrer, M.Whitlow, M.Adler, S.Finster, Z.Chang, and D.O.Arnaiz (2005).
Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1.
  J Biol Chem, 280, 19867-19874.
PDB code: 1z5m
15123247 C.McInnes, S.Wang, S.Anderson, J.O'Boyle, W.Jackson, G.Kontopidis, C.Meades, M.Mezna, M.Thomas, G.Wood, D.P.Lane, and P.M.Fischer (2004).
Structural determinants of CDK4 inhibition and design of selective ATP competitive inhibitors.
  Chem Biol, 11, 525-534.  
15505811 H.Park, M.S.Yeom, and S.Lee (2004).
Loop flexibility and solvent dynamics as determinants for the selective inhibition of cyclin-dependent kinase 4: comparative molecular dynamics simulation studies of CDK2 and CDK4.
  Chembiochem, 5, 1662-1672.  
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. Where a reference describes a PDB structure, the PDB codes are shown on the right.