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PDBsum entry 1pf8

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Transferase PDB id
1pf8
Jmol
Contents
Protein chain
298 a.a. *
Ligands
SU9
* Residue conservation analysis
PDB id:
1pf8
Name: Transferase
Title: Crystal structure of human cyclin-dependent kinase 2 complex nucleoside inhibitor
Structure: Cell division protein kinase 2. Chain: a. Synonym: p33 protein kinase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: cdk2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Resolution:
2.51Å     R-factor:   0.208     R-free:   0.306
Authors: D.J.Moshinsky,R.C.Bellamacina,D.C.Boisvert,P.Huang,T.Hui,J.J S.H.Kim,A.G.Rice
Key ref: D.J.Moshinsky et al. (2003). SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2. Biochem Biophys Res Commun, 310, 1026-1031. PubMed id: 14550307 DOI: 10.1016/j.bbrc.2003.09.114
Date:
24-May-03     Release date:   23-Dec-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
298 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.bbrc.2003.09.114 Biochem Biophys Res Commun 310:1026-1031 (2003)
PubMed id: 14550307  
 
 
SU9516: biochemical analysis of cdk inhibition and crystal structure in complex with cdk2.
D.J.Moshinsky, C.R.Bellamacina, D.C.Boisvert, P.Huang, T.Hui, J.Jancarik, S.H.Kim, A.G.Rice.
 
  ABSTRACT  
 
SU9516 is a 3-substituted indolinone compound with demonstrated potent and selective inhibition toward cyclin dependent kinases (cdks). Here, we describe the kinetic characterization of this inhibition with respect to cdk2, 1, and 4, along with the crystal structure in complex with cdk2. The molecule is competitive with respect to ATP for cdk2/cyclin A, with a K(i) value of 0.031 microM. Similarly, SU9516 inhibits cdk2/cyclin E and cdk1/cyclin B1 in an ATP-competitive manner, although at a 2- to 8-fold reduced potency. In contrast, the compound exhibited non-competitive inhibition with respect to ATP toward cdk4/cyclin D1, with a 45-fold reduced potency. The X-ray crystal structure of SU9516 bound to cdk2 revealed interactions between the molecule and Leu83 and Glu81 of the kinase. This study should aid in the development of more potent and selective cdk inhibitors for potential therapeutic agents.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19139818 X.Xiong, Y.Zhang, X.Gao, Z.Dong, L.Li, C.Ji, L.Fu, X.Luo, H.Liu, and C.Mei (2010).
B5, a novel pyrrole-substituted indolinone, exerts potent antitumor efficacy through G2/M cell cycle arrest.
  Invest New Drugs, 28, 26-34.  
18408713 A.Degterev, J.Hitomi, M.Germscheid, I.L.Ch'en, O.Korkina, X.Teng, D.Abbott, G.D.Cuny, C.Yuan, G.Wagner, S.M.Hedrick, S.A.Gerber, A.Lugovskoy, and J.Yuan (2008).
Identification of RIP1 kinase as a specific cellular target of necrostatins.
  Nat Chem Biol, 4, 313-321.  
17704657 M.Sassatelli, F.Bouchikhi, B.Aboab, F.Anizon, D.Fabbro, M.Prudhomme, and P.Moreau (2007).
In-vitro antiproliferative activities and kinase inhibitory potencies of glycosyl-isoindigo derivatives.
  Anticancer Drugs, 18, 1069-1074.  
17463001 S.Kobayashi, S.H.Lee, X.W.Meng, J.L.Mott, S.F.Bronk, N.W.Werneburg, R.W.Craig, S.H.Kaufmann, and G.J.Gores (2007).
Serine 64 phosphorylation enhances the antiapoptotic function of Mcl-1.
  J Biol Chem, 282, 18407-18417.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
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.