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PDBsum entry 1g5s

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protein ligands links
Cell cycle/transferase PDB id
1g5s
Jmol
Contents
Protein chain
275 a.a. *
Ligands
I17
Waters ×30
* Residue conservation analysis
PDB id:
1g5s
Name: Cell cycle/transferase
Title: Crystal structure of human cyclin dependent kinase 2 (cdk2) in complex with the inhibitor h717
Structure: Cell division protein kinase 2. Chain: a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.
Resolution:
2.61Å     R-factor:   0.201     R-free:   0.242
Authors: M.K.Dreyer,D.R.Borcherding,J.A.Dumont,N.P.Peet,J.T.Tsay, P.S.Wright,A.J.Bitonti,J.Shen,S.-H.Kim
Key ref: M.K.Dreyer et al. (2001). Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717. J Med Chem, 44, 524-530. PubMed id: 11170642 DOI: 10.1021/jm001043t
Date:
02-Nov-00     Release date:   02-Nov-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
275 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: 10.1021/jm001043t J Med Chem 44:524-530 (2001)
PubMed id: 11170642  
 
 
Crystal structure of human cyclin-dependent kinase 2 in complex with the adenine-derived inhibitor H717.
M.K.Dreyer, D.R.Borcherding, J.A.Dumont, N.P.Peet, J.T.Tsay, P.S.Wright, A.J.Bitonti, J.Shen, S.H.Kim.
 
  ABSTRACT  
 
Cyclin-dependent kinases (CDKs) are regulatory proteins of the eukaryotic cell cycle. They act after association with different cyclins, the concentrations of which vary throughout the progression of the cell cycle. As central mediators of cell growth, CDKs are potential targets for inhibitory molecules that would allow disruption of the cell cycle in order to evoke an antiproliferative effect and may therefore be useful as cancer therapeutics. We synthesized several inhibitory 2,6,9-trisubstituted purine derivatives and solved the crystal structure of one of these compounds, H717, in complex with human CDK2 at 2.6 A resolution. The orientation of the C2-p-diaminocyclohexyl portion of the inhibitor is strikingly different from those of similar moieties in other related inhibitor complexes. The N9-cyclopentyl ring fully occupies a space in the enzyme which is otherwise empty, while the C6-N-aminobenzyl substituent points out of the ATP-binding site. The structure provides a basis for the further development of more potent inhibitory drugs.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
17541419 M.P.Mazanetz, and P.M.Fischer (2007).
Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases.
  Nat Rev Drug Discov, 6, 464-479.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
15993080 L.Havlicek, K.Fuksova, V.Krystof, M.Orsag, B.Vojtesek, and M.Strnad (2005).
8-Azapurines as new inhibitors of cyclin-dependent kinases.
  Bioorg Med Chem, 13, 5399-5407.  
12869192 E.De Moliner, N.R.Brown, and L.N.Johnson (2003).
Alternative binding modes of an inhibitor to two different kinases.
  Eur J Biochem, 270, 3174-3181.
PDB code: 1p5e
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.  
11344036 A.Westwell (2001).
Novel antitumour molecules.
  Drug Discov Today, 6, 489-491.  
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 code is shown on the right.