PDBsum entry 1ke5

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protein ligands links
Transferase PDB id
Protein chain
281 a.a. *
Waters ×134
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Cdk2 complexed with n-methyl-4-{[(2-oxo-1,2-dihydro-3h- indol-3-ylidene)methyl]amino}benzenesulfonamide
Structure: Cell division protein kinase 2. Chain: a. Synonym: cdk2, p33 protein kinase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
2.20Å     R-factor:   0.184     R-free:   0.224
Authors: H.N.Bramson,J.Corona,S.T.Davis,S.H.Dickerson,M.Edelstein, S.V.Frye,R.T.Gampe,A.M.Hassell,L.M.Shewchuk,L.F.Kuyper
Key ref: H.N.Bramson et al. (2001). Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis. J Med Chem, 44, 4339-4358. PubMed id: 11728181 DOI: 10.1021/jm010117d
14-Nov-01     Release date:   14-May-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
298 a.a.
281 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Cyclin-dependent kinase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + a protein = ADP + a phosphoprotein
+ protein
+ 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   28 terms 
  Biochemical function     nucleotide binding     12 terms  


DOI no: 10.1021/jm010117d J Med Chem 44:4339-4358 (2001)
PubMed id: 11728181  
Oxindole-based inhibitors of cyclin-dependent kinase 2 (CDK2): design, synthesis, enzymatic activities, and X-ray crystallographic analysis.
H.N.Bramson, J.Corona, S.T.Davis, S.H.Dickerson, M.Edelstein, S.V.Frye, R.T.Gampe, P.A.Harris, A.Hassell, W.D.Holmes, R.N.Hunter, K.E.Lackey, B.Lovejoy, M.J.Luzzio, V.Montana, W.J.Rocque, D.Rusnak, L.Shewchuk, J.M.Veal, D.H.Walker, L.F.Kuyper.
Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency approximately 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21472162 C.R.Reddy, E.Jithender, G.Krishna, G.V.Reddy, and B.Jagadeesh (2011).
A novel acid-catalyzed C5-alkylation of oxindoles using alcohols.
  Org Biomol Chem, 9, 3940-3947.  
20601979 B.V.Silva, N.M.Ribeiro, M.D.Vargas, M.Lanznaster, J.W.Carneiro, R.Krogh, A.D.Andricopulo, L.C.Dias, and A.C.Pinto (2010).
Synthesis, electrochemical studies and anticancer activity of ferrocenyl oxindoles.
  Dalton Trans, 39, 7338-7344.  
20575139 K.Engels, C.Beyer, M.L.Suárez Fernández, F.Bender, M.Gassel, G.Unden, R.J.Marhöfer, J.C.Mottram, and P.M.Selzer (2010).
Inhibition of Eimeria tenella CDK-related kinase 2: From target identification to lead compounds.
  ChemMedChem, 5, 1259-1271.  
18855677 A.Bakan, J.S.Lazo, P.Wipf, K.M.Brummond, and I.Bahar (2008).
Toward a molecular understanding of the interaction of dual specificity phosphatases with substrates: insights from structure-based modeling and high throughput screening.
  Curr Med Chem, 15, 2536-2544.  
18680359 H.R.Lawrence, R.Pireddu, L.Chen, Y.Luo, S.S.Sung, A.M.Szymanski, M.L.Yip, W.C.Guida, S.M.Sebti, J.Wu, and N.J.Lawrence (2008).
Inhibitors of Src homology-2 domain containing protein tyrosine phosphatase-2 (Shp2) based on oxindole scaffolds.
  J Med Chem, 51, 4948-4956.  
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.  
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.  
16444268 A.D.Pyle, L.F.Lock, and P.J.Donovan (2006).
Neurotrophins mediate human embryonic stem cell survival.
  Nat Biotechnol, 24, 344-350.  
16632252 C.Kung, D.M.Kenski, K.Krukenberg, H.D.Madhani, and K.M.Shokat (2006).
Selective kinase inhibition by exploiting differential pathway sensitivity.
  Chem Biol, 13, 399-407.  
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.  
15738404 C.Kung, D.M.Kenski, S.H.Dickerson, R.W.Howson, L.F.Kuyper, H.D.Madhani, and K.M.Shokat (2005).
Chemical genomic profiling to identify intracellular targets of a multiplex kinase inhibitor.
  Proc Natl Acad Sci U S A, 102, 3587-3592.  
15931503 H.Dureja, and A.K.Madan (2005).
Topochemical models for prediction of cyclin-dependent kinase 2 inhibitory activity of indole-2-ones.
  J Mol Model, 11, 525-531.  
12556199 N.C.Waters, and J.A.Geyer (2003).
Cyclin-dependent protein kinases as therapeutic drug targets for antimalarial drug development.
  Expert Opin Ther Targets, 7, 7.  
11927285 E.A.Sausville (2002).
Complexities in the development of cyclin-dependent kinase inhibitor drugs.
  Trends Mol Med, 8, S32-S37.  
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.