PDBsum entry 1pxi

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Transferase PDB id
Protein chain
294 a.a. *
Waters ×251
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Human cyclin dependent kinase 2 complexed with the inhibitor 4-(2,5-dichloro-thiophen-3-yl)-pyrimidin-2- ylamine
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.
1.95Å     R-factor:   0.203     R-free:   0.251
Authors: S.Y.Wu,I.Mcnae,G.Kontopidis,S.J.Mcclue,C.Mcinnes, K.J.Stewart,S.Wang,D.I.Zheleva,H.Marriage,D.P.Lane,P.Taylor P.M.Fischer,M.D.Walkinshaw
Key ref:
S.Y.Wu et al. (2003). Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop. Structure, 11, 399-410. PubMed id: 12679018
04-Jul-03     Release date:   09-Dec-03    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
298 a.a.
294 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  


Structure 11:399-410 (2003)
PubMed id: 12679018  
Discovery of a novel family of CDK inhibitors with the program LIDAEUS: structural basis for ligand-induced disordering of the activation loop.
S.Y.Wu, I.McNae, G.Kontopidis, S.J.McClue, C.McInnes, K.J.Stewart, S.Wang, D.I.Zheleva, H.Marriage, D.P.Lane, P.Taylor, P.M.Fischer, M.D.Walkinshaw.
A family of 4-heteroaryl-2-amino-pyrimidine CDK2 inhibitor lead compounds was discovered with the new database-mining program LIDAEUS through in silico screening. Four compounds with IC(50) values ranging from 17 to 0.9 microM were selected for X-ray crystal analysis. Two distinct binding modes are observed, one of which resembles the hydrogen bonding pattern of bound ATP. In the second binding mode, the ligands trigger a conformational change in the activation T loop by inducing movement of Lys(33) and Asp(145) side chains. The family of molecules discovered provides an excellent starting point for the design and synthesis of tight binding inhibitors, which may lead to a new class of antiproliferative drugs.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21286784 P.Dobeš, J.Fanfrlík, J.Rezáč, M.Otyepka, and P.Hobza (2011).
Transferable scoring function based on semiempirical quantum mechanical PM6-DH2 method: CDK2 with 15 structurally diverse inhibitors.
  J Comput Aided Mol Des, 25, 223-235.  
21035734 S.Wang, G.Griffiths, C.A.Midgley, A.L.Barnett, M.Cooper, J.Grabarek, L.Ingram, W.Jackson, G.Kontopidis, S.J.McClue, C.McInnes, J.McLachlan, C.Meades, M.Mezna, I.Stuart, M.P.Thomas, D.I.Zheleva, D.P.Lane, R.C.Jackson, D.M.Glover, D.G.Blake, and P.M.Fischer (2010).
Discovery and characterization of 2-anilino-4- (thiazol-5-yl)pyrimidine transcriptional CDK inhibitors as anticancer agents.
  Chem Biol, 17, 1111-1121.
PDB codes: 2xmy 2xnb
19472269 G.Kontopidis, M.J.Andrews, C.McInnes, A.Plater, L.Innes, S.Renachowski, A.Cowan, and P.M.Fischer (2009).
Truncation and optimisation of peptide inhibitors of cyclin-dependent kinase 2-cyclin a through structure-guided design.
  ChemMedChem, 4, 1120-1128.
PDB codes: 2wev 2wfy 2whb
18093984 L.Zhang, W.Liu, T.Hu, L.Du, C.Luo, K.Chen, X.Shen, and H.Jiang (2008).
Structural basis for catalytic and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ).
  J Biol Chem, 283, 5370-5379.
PDB codes: 2gll 2glm 2glp 2glv
18037925 N.Moitessier, P.Englebienne, D.Lee, J.Lawandi, and C.R.Corbeil (2008).
Towards the development of universal, fast and highly accurate docking/scoring methods: a long way to go.
  Br J Pharmacol, 153, S7-26.  
18037921 P.Taylor, E.Blackburn, Y.G.Sheng, S.Harding, K.Y.Hsin, D.Kan, S.Shave, and M.D.Walkinshaw (2008).
Ligand discovery and virtual screening using the program LIDAEUS.
  Br J Pharmacol, 153, S55-S67.  
18405842 W.Muster, A.Breidenbach, H.Fischer, S.Kirchner, L.Müller, and A.Pähler (2008).
Computational toxicology in drug development.
  Drug Discov Today, 13, 303-310.  
17936059 C.McInnes (2007).
Virtual screening strategies in drug discovery.
  Curr Opin Chem Biol, 11, 494-502.  
17339323 L.Spíchal, V.Krystof, M.Paprskárová, R.Lenobel, J.Styskala, P.Binarová, V.Cenklová, L.De Veylder, D.Inzé, G.Kontopidis, P.M.Fischer, T.Schmülling, and M.Strnad (2007).
Classical anticytokinins do not interact with cytokinin receptors but inhibit cyclin-dependent kinases.
  J Biol Chem, 282, 14356-14363.  
16580603 A.J.Orry, R.A.Abagyan, and C.N.Cavasotto (2006).
Structure-based development of target-specific compound libraries.
  Drug Discov Today, 11, 261-266.  
17028581 C.McInnes, A.Mazumdar, M.Mezna, C.Meades, C.Midgley, F.Scaerou, L.Carpenter, M.Mackenzie, P.Taylor, M.Walkinshaw, P.M.Fischer, and D.Glover (2006).
Inhibitors of Polo-like kinase reveal roles in spindle-pole maintenance.
  Nat Chem Biol, 2, 608-617.  
16708364 E.Perola (2006).
Minimizing false positives in kinase virtual screens.
  Proteins, 64, 422-435.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
16557283 K.Strebhardt, and A.Ullrich (2006).
Targeting polo-like kinase 1 for cancer therapy.
  Nat Rev Cancer, 6, 321-330.  
17051658 M.J.Andrews, G.Kontopidis, C.McInnes, A.Plater, L.Innes, A.Cowan, P.Jewsbury, and P.M.Fischer (2006).
REPLACE: a strategy for iterative design of cyclin-binding groove inhibitors.
  Chembiochem, 7, 1909-1915.
PDB codes: 2uue 2v22
17001081 N.Canela, M.Orzáez, R.Fucho, F.Mateo, R.Gutierrez, A.Pineda-Lucena, O.Bachs, and E.Pérez-Payá (2006).
Identification of an hexapeptide that binds to a surface pocket in cyclin A and inhibits the catalytic activity of the complex cyclin-dependent kinase 2-cyclin A.
  J Biol Chem, 281, 35942-35953.  
19617922 P.M.Fischer (2006).
Peptide, Peptidomimetic, and Small-molecule Antagonists of the p53-HDM2 Protein-Protein Interaction.
  Int J Pept Res Ther, 12, 3.  
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.  
15288245 J.C.Alvarez (2004).
High-throughput docking as a source of novel drug leads.
  Curr Opin Chem Biol, 8, 365-370.  
12783608 P.M.Fischer (2003).
CNIO cancer conference: targeted search for anticancer drugs.
  Expert Opin Investig Drugs, 12, 1039-1044.  
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.