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PDBsum entry 2a4l

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protein ligands links
Transferase PDB id
2a4l
Jmol
Contents
Protein chain
286 a.a. *
Ligands
RRC
Waters ×82
* Residue conservation analysis
PDB id:
2a4l
Name: Transferase
Title: Human cyclin-dependent kinase 2 in complex with roscovitine
Structure: Homo sapiens cyclin-dependent kinase 2. Chain: a. Synonym: cdk2. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9 cells.
Resolution:
2.40Å     R-factor:   0.173     R-free:   0.270
Authors: W.F.De Azevedo Jr.,S.H.Kim
Key ref: W.F.De Azevedo et al. (1997). Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Eur J Biochem, 243, 518-526. PubMed id: 9030780
Date:
29-Jun-05     Release date:   03-Oct-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
286 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   14 terms 
  Biological process     regulation of gene silencing   27 terms 
  Biochemical function     nucleotide binding     12 terms  

 

 
    reference    
 
 
Eur J Biochem 243:518-526 (1997)
PubMed id: 9030780  
 
 
Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine.
W.F.De Azevedo, S.Leclerc, L.Meijer, L.Havlicek, M.Strnad, S.H.Kim.
 
  ABSTRACT  
 
Cyclin-dependent kinases (cdk) control the cell division cycle (cdc). These kinases and their regulators are frequently deregulated in human tumours. A potent inhibitor of cdks, roscovitine [2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurin e], was identified by screening a series of C2,N6,N9-substituted adenines on purified cdc2/cyclin B. Roscovitine displays high efficiency and high selectivity (Meijer, L., Borgne, A., Mulner, O., Chong, J. P. J., Blow, J. J., Inagaki, N., Inagaki, M., Delcros, J.-G. & Moulinoux, J.-P. (1997) Eur. J. Biochem. 243, 527-536). It behaves as a competitive inhibitor for ATP binding to cdc2. We determined the crystal structure of a complex between cdk2 and roscovitine at 0.24-nm (2.4 A) resolution and refined to an Rfactor of 0.18. The purine portion of the inhibitor binds to the adenine binding pocket of cdk2. The position of the benzyl ring group of the inhibitor enables the inhibitor to make contacts with the enzyme not observed in the ATP-complex structure. Analysis of the position of this benzyl ring explains the specificity of roscovitine in inhibiting cdk2. The structure also reveals that the (R)-stereoisomer of roscovitine is bound to cdk2. The (R)-isomer is about twice as potent in inhibiting cdc2/cyclin B than the (S)-isomer. Results from structure/activity studies and from analysis of the cdk2/roscovitine complex crystal structure should allow the design of even more potent cdk inhibitors.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21328450 J.Węsierska-Gądek, D.Gritsch, N.Zulehner, O.Komina, and M.Maurer (2011).
Roscovitine, a selective CDK inhibitor, reduces the basal and estrogen-induced phosphorylation of ER-α in human ER-positive breast cancer cells.
  J Cell Biochem, 112, 761-772.  
21308739 J.Węsierska-Gądek, D.Gritsch, N.Zulehner, O.Komina, and M.Maurer (2011).
Interference with ER-α enhances the therapeutic efficacy of the selective CDK inhibitor roscovitine towards ER-positive breast cancer cells.
  J Cell Biochem, 112, 1103-1117.  
20836132 J.Węsierska-Gądek, M.Maurer, N.Zulehner, and O.Komina (2011).
Whether to target single or multiple CDKs for therapy? That is the question.
  J Cell Physiol, 226, 341-349.  
21080333 J.Węsierska-Gądek, S.Hackl, N.Zulehner, M.Maurer, and O.Komina (2011).
Reconstitution of human MCF-7 breast cancer cells with caspase-3 does not sensitize them to action of CDK inhibitors.
  J Cell Biochem, 112, 273-288.  
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.  
21253554 R.Conyers, S.Young, and D.M.Thomas (2011).
Liposarcoma: molecular genetics and therapeutics.
  Sarcoma, 2011, 483154.  
21087997 V.Quennet, A.Beucher, O.Barton, S.Takeda, and M.Löbrich (2011).
CtIP and MRN promote non-homologous end-joining of etoposide-induced DNA double-strand breaks in G1.
  Nucleic Acids Res, 39, 2144-2152.  
20013135 B.Zhang, Z.C.Su, T.E.Tay, and V.B.Tan (2010).
Mechanism of CDK5 activation revealed by steered molecular dynamics simulations and energy calculations.
  J Mol Model, 16, 1159-1168.  
20448906 C.Wong, R.J.Griffin, I.R.Hardcastle, J.S.Northen, L.Z.Wang, and B.T.Golding (2010).
Synthesis of sulfonamide-based kinase inhibitors from sulfonates by exploiting the abrogated SN2 reactivity of 2,2,2-trifluoroethoxysulfonates.
  Org Biomol Chem, 8, 2457-2464.  
20450234 C.X.Gong, I.Grundke-Iqbal, and K.Iqbal (2010).
Targeting tau protein in Alzheimer's disease.
  Drugs Aging, 27, 351-365.  
20028770 F.Galimberti, S.L.Thompson, X.Liu, H.Li, V.Memoli, S.R.Green, J.DiRenzo, P.Greninger, S.V.Sharma, J.Settleman, D.A.Compton, and E.Dmitrovsky (2010).
Targeting the cyclin E-Cdk-2 complex represses lung cancer growth by triggering anaphase catastrophe.
  Clin Cancer Res, 16, 109-120.  
20959006 J.B.Stevens, B.Y.Abdallah, S.M.Regan, G.Liu, S.W.Bremer, C.J.Ye, and H.H.Heng (2010).
Comparison of mitotic cell death by chromosome fragmentation to premature chromosome condensation.
  Mol Cytogenet, 3, 20.  
  20054100 J.Holcakova, P.Tomasec, J.J.Bugert, E.C.Wang, G.W.Wilkinson, R.Hrstka, V.Krystof, M.Strnad, and B.Vojtesek (2010).
The inhibitor of cyclin-dependent kinases, olomoucine II, exhibits potent antiviral properties.
  Antivir Chem Chemother, 20, 133-142.  
20889493 M.Morita, K.Hamao, S.Izumi, E.Okumura, K.Tanaka, T.Kishimoto, and H.Hosoya (2010).
Proline-rich domain in dynamin-2 has a low microtubule-binding activity: how is this activity controlled during mitosis in HeLa cells?
  J Biochem, 148, 533-538.  
19174463 A.Grob, P.Roussel, J.E.Wright, B.McStay, D.Hernandez-Verdun, and V.Sirri (2009).
Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis.
  J Cell Sci, 122, 489-498.  
19297489 A.J.Kapasi, C.L.Clark, K.Tran, and D.H.Spector (2009).
Recruitment of cdk9 to the immediate-early viral transcriptosomes during human cytomegalovirus infection requires efficient binding to cyclin T1, a threshold level of IE2 86, and active transcription.
  J Virol, 83, 5904-5917.  
19415659 D.Raffa, B.Maggio, S.Cascioferro, M.V.Raimondi, G.Daidone, S.Plescia, D.Schillaci, M.G.Cusimano, L.Titone, C.Colomba, and M.Tolomeo (2009).
N-(indazolyl)benzamido derivatives as CDK1 inhibitors: design, synthesis, biological activity, and molecular docking studies.
  Arch Pharm (Weinheim), 342, 265-273.  
19043750 G.B.Barcellos, R.A.Caceres, and W.F.de Azevedo (2009).
Structural studies of shikimate dehydrogenase from Bacillus anthracis complexed with cofactor NADP.
  J Mol Model, 15, 147-155.  
19723060 J.Wesierska-Gadek, and V.Krystof (2009).
Selective cyclin-dependent kinase inhibitors discriminating between cell cycle and transcriptional kinases: future reality or utopia?
  Ann N Y Acad Sci, 1171, 228-241.  
19723062 M.Maurer, O.Komina, and J.Wesierska-Gadek (2009).
Roscovitine differentially affects asynchronously growing and synchronized human MCF-7 breast cancer cells.
  Ann N Y Acad Sci, 1171, 250-256.  
19039815 M.Orzáez, A.Gortat, L.Mondragón, O.Bachs, and E.Pérez-Payá (2009).
ATP-noncompetitive inhibitors of CDK-cyclin complexes.
  ChemMedChem, 4, 19-24.  
21581908 M.Rouchal, M.Nečas, F.P.de Carvalho, and R.Vícha (2009).
2-(1-Adamant-yl)-1-{4-[(2-chloro-9-isopropyl-9H-purin-6-yl)amino-meth-yl]phen-yl}ethanone.
  Acta Crystallogr Sect E Struct Rep Online, 65, o298-o299.  
19003963 M.V.Appleyard, M.A.O'Neill, K.E.Murray, F.E.Paulin, S.E.Bray, N.M.Kernohan, D.A.Levison, D.P.Lane, and A.M.Thompson (2009).
Seliciclib (CYC202, R-roscovitine) enhances the antitumor effect of doxorubicin in vivo in a breast cancer xenograft model.
  Int J Cancer, 124, 465-472.  
19244476 S.B.Ganapathi, M.Kester, and K.S.Elmslie (2009).
State-dependent block of HERG potassium channels by R-roscovitine: implications for cancer therapy.
  Am J Physiol Cell Physiol, 296, C701-C710.  
19723061 S.Wandl, and J.Wesierska-Gadek (2009).
Is olomoucine, a weak CDK2 inhibitor, able to induce apoptosis in cancer cells?
  Ann N Y Acad Sci, 1171, 242-249.  
19619927 W.Wang, B.Bu, M.Xie, M.Zhang, Z.Yu, and D.Tao (2009).
Neural cell cycle dysregulation and central nervous system diseases.
  Prog Neurobiol, 89, 1.  
19028587 X.Huang, P.Finerty, J.R.Walker, C.Butler-Cole, M.Vedadi, M.Schapira, S.A.Parker, B.E.Turk, D.A.Thompson, and S.Dhe-Paganon (2009).
Structural insights into the inhibited states of the Mer receptor tyrosine kinase.
  J Struct Biol, 165, 88-96.
PDB codes: 2p0c 3bpr 3brb
19687009 X.Yang, H.Li, X.S.Liu, A.Deng, and X.Liu (2009).
Cdc2-mediated phosphorylation of CLIP-170 is essential for its inhibition of centrosome reduplication.
  J Biol Chem, 284, 28775-28782.  
17942543 A.J.Kapasi, and D.H.Spector (2008).
Inhibition of the cyclin-dependent kinases at the beginning of human cytomegalovirus infection specifically alters the levels and localization of the RNA polymerase II carboxyl-terminal domain kinases cdk9 and cdk7 at the viral transcriptosome.
  J Virol, 82, 394-407.  
18171934 B.Langley, M.A.D'Annibale, K.Suh, I.Ayoub, A.Tolhurst, B.Bastan, L.Yang, B.Ko, M.Fisher, S.Cho, M.F.Beal, and R.R.Ratan (2008).
Pulse inhibition of histone deacetylases induces complete resistance to oxidative death in cortical neurons without toxicity and reveals a role for cytoplasmic p21(waf1/cip1) in cell cycle-independent neuroprotection.
  J Neurosci, 28, 163-176.  
18855662 C.X.Gong, and K.Iqbal (2008).
Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease.
  Curr Med Chem, 15, 2321-2328.  
17926351 D.Han, B.T.Zhao, Y.Liu, J.J.Li, Y.G.Wu, G.C.Lan, and J.H.Tan (2008).
Interactive effects of low temperature and roscovitine (ROS) on meiotic resumption and developmental potential of goat oocytes.
  Mol Reprod Dev, 75, 838-846.  
19032760 D.R.Caffrey, E.A.Lunney, and D.J.Moshinsky (2008).
Prediction of specificity-determining residues for small-molecule kinase inhibitors.
  BMC Bioinformatics, 9, 491.  
19046382 H.M.Chen, L.Wang, and S.R.D'Mello (2008).
A chemical compound commonly used to inhibit PKR, {8-(imidazol-4-ylmethylene)-6H-azolidino[5,4-g] benzothiazol-7-one}, protects neurons by inhibiting cyclin-dependent kinase.
  Eur J Neurosci, 28, 2003-2016.  
18042686 I.Bártová, J.Koca, and M.Otyepka (2008).
Functional flexibility of human cyclin-dependent kinase-2 and its evolutionary conservation.
  Protein Sci, 17, 22-33.  
19119451 K.C.Shin, C.G.Park, E.S.Hwang, and C.Y.Cha (2008).
Human Cytomegalovirus IE1 Protein Enhances Herpes Simplex Virus Type 1-induced Syncytial Formation in U373MG Cells.
  J Korean Med Sci, 23, 1046-1052.  
17942546 K.Tran, J.A.Mahr, J.Choi, J.G.Teodoro, M.R.Green, and D.H.Spector (2008).
Accumulation of substrates of the anaphase-promoting complex (APC) during human cytomegalovirus infection is associated with the phosphorylation of Cdh1 and the dissociation and relocalization of APC subunits.
  J Virol, 82, 529-537.  
18181150 M.K.Jones, O.R.Padilla, N.A.Webb, and M.Norng (2008).
The anti-apoptosis protein, survivin, mediates gastric epithelial cell cytoprotection against ethanol-induced injury via activation of the p34(cdc2) cyclin-dependent kinase.
  J Cell Physiol, 215, 750-764.  
18490441 M.M.Koseoglu, L.M.Graves, and W.F.Marzluff (2008).
Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase.
  Mol Cell Biol, 28, 4469-4479.  
18777593 M.S.Abaza, A.M.Bahman, and R.J.Al-Attiyah (2008).
Roscovitine synergizes with conventional chemo-therapeutic drugs to induce efficient apoptosis of human colorectal cancer cells.
  World J Gastroenterol, 14, 5162-5175.  
18778306 M.Zhang, J.L.Hallows, X.Wang, B.Bu, W.Wang, and I.Vincent (2008).
Mitogen-activated protein kinase activity may not be necessary for the neuropathology of Niemann-Pick type C mice.
  J Neurochem, 107, 814-822.  
18370874 P.C.Wu, M.H.Tai, D.N.Hu, C.H.Lai, Y.H.Chen, Y.C.Wu, C.L.Tsai, S.J.Shin, and H.K.Kuo (2008).
Cyclin-dependent kinase inhibitor roscovitine induces cell cycle arrest and apoptosis in rabbit retinal pigment epithelial cells.
  J Ocul Pharmacol Ther, 24, 25-33.  
18356301 Q.Kan, S.Jinno, H.Yamamoto, K.Kobayashi, and H.Okayama (2008).
ATP-dependent activation of p21WAF1/CIP1-associated Cdk2 by Cdc6.
  Proc Natl Acad Sci U S A, 105, 4757-4762.  
18501396 S.C.McNeely, B.F.Taylor, and J.C.States (2008).
Mitotic arrest-associated apoptosis induced by sodium arsenite in A375 melanoma cells is BUBR1-dependent.
  Toxicol Appl Pharmacol, 231, 61-67.  
17937404 T.O.Fischmann, A.Hruza, J.S.Duca, L.Ramanathan, T.Mayhood, W.T.Windsor, H.V.Le, T.J.Guzi, M.P.Dwyer, K.Paruch, R.J.Doll, E.Lees, D.Parry, W.Seghezzi, and V.Madison (2008).
Structure-guided discovery of cyclin-dependent kinase inhibitors.
  Biopolymers, 89, 372-379.
PDB codes: 2r3f 2r3g 2r3h 2r3i 2r3j 2r3k 2r3l 2r3m 2r3n 2r3o 2r3p 2r3q 2r3r
  18769144 Y.Huang, T.Sen, J.Nagpal, S.Upadhyay, B.Trink, E.Ratovitski, and D.Sidransky (2008).
ATM kinase is a master switch for the Delta Np63 alpha phosphorylation/degradation in human head and neck squamous cell carcinoma cells upon DNA damage.
  Cell Cycle, 7, 2846-2855.  
18221369 Z.Buraei, and K.S.Elmslie (2008).
The separation of antagonist from agonist effects of trisubstituted purines on CaV2.2 (N-type) channels.
  J Neurochem, 105, 1450-1461.  
17846426 A.Errico, V.Costanzo, and T.Hunt (2007).
Tipin is required for stalled replication forks to resume DNA replication after removal of aphidicolin in Xenopus egg extracts.
  Proc Natl Acad Sci U S A, 104, 14929-14934.  
16770643 B.Zhang, V.B.Tan, K.M.Lim, T.E.Tay, and S.Zhuang (2007).
Study of the inhibition of cyclin-dependent kinases with roscovitine and indirubin-3'-oxime from molecular dynamics simulations.
  J Mol Model, 13, 79-89.  
17179992 C.Benson, J.White, J.De Bono, A.O'Donnell, F.Raynaud, C.Cruickshank, H.McGrath, M.Walton, P.Workman, S.Kaye, J.Cassidy, A.Gianella-Borradori, I.Judson, and C.Twelves (2007).
A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days.
  Br J Cancer, 96, 29-37.  
17225251 D.Guiffant, D.Tribouillard, F.Gug, H.Galons, L.Meijer, M.Blondel, and S.Bach (2007).
Identification of intracellular targets of small molecular weight chemical compounds using affinity chromatography.
  Biotechnol J, 2, 68-75.  
17318617 H.Song, M.Vita, H.Sallam, R.Tehranchi, C.Nilsson, A.Sidén, and Z.Hassan (2007).
Effect of the Cdk-inhibitor roscovitine on mouse hematopoietic progenitors in vivo and in vitro.
  Cancer Chemother Pharmacol, 60, 841-849.  
17085505 J.H.Alzate-Morales, R.Contreras, A.Soriano, I.Tuñon, and E.Silla (2007).
A computational study of the protein-ligand interactions in CDK2 inhibitors: using quantum mechanics/molecular mechanics interaction energy as a predictor of the biological activity.
  Biophys J, 92, 430-439.  
17975794 J.Wesierska-Gadek, M.Gueorguieva, M.P.Kramer, C.Ranftler, B.Sarg, and H.Lindner (2007).
A new, unexpected action of olomoucine, a CDK inhibitor, on normal human cells: up-regulation of CLIMP-63, a cytoskeleton-linking membrane protein.
  J Cell Biochem, 102, 1405-1419.  
17203463 J.Wesierska-Gadek, M.L.Schmitz, and C.Ranftler (2007).
Roscovitine-activated HIP2 kinase induces phosphorylation of wt p53 at Ser-46 in human MCF-7 breast cancer cells.
  J Cell Biochem, 100, 865-874.  
17415788 J.Wesierska-Gadek, M.Maurer, and G.Schmid (2007).
Inhibition of farnesyl protein transferase sensitizes human MCF-7 breast cancer cells to roscovitine-mediated cell cycle arrest.
  J Cell Biochem, 102, 736-747.  
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.  
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.  
16951685 A.G.Rossi, D.A.Sawatzky, A.Walker, C.Ward, T.A.Sheldrake, N.A.Riley, A.Caldicott, M.Martinez-Losa, T.R.Walker, R.Duffin, M.Gray, E.Crescenzi, M.C.Martin, H.J.Brady, J.S.Savill, I.Dransfield, and C.Haslett (2006).
Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis.
  Nat Med, 12, 1056-1064.  
16327781 A.Jazayeri, J.Falck, C.Lukas, J.Bartek, G.C.Smith, J.Lukas, and S.P.Jackson (2006).
ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks.
  Nat Cell Biol, 8, 37-45.  
16158051 A.Krystyniak, C.Garcia-Echeverria, C.Prigent, and S.Ferrari (2006).
Inhibition of Aurora A in response to DNA damage.
  Oncogene, 25, 338-348.  
17054019 B.Zhang, V.B.Tan, K.M.Lim, and T.E.Tay (2006).
Molecular dynamics simulations on the inhibition of cyclin-dependent kinases 2 and 5 in the presence of activators.
  J Comput Aided Mol Des, 20, 395-404.  
16492148 D.Dalgarno, T.Stehle, S.Narula, P.Schelling, M.R.van Schravendijk, S.Adams, L.Andrade, J.Keats, M.Ram, L.Jin, T.Grossman, I.MacNeil, C.Metcalf, W.Shakespeare, Y.Wang, T.Keenan, R.Sundaramoorthi, R.Bohacek, M.Weigele, and T.Sawyer (2006).
Structural basis of Src tyrosine kinase inhibition with a new class of potent and selective trisubstituted purine-based compounds.
  Chem Biol Drug Des, 67, 46-57.
PDB codes: 2bdf 2bdj
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
16741967 J.Wesierska-Gadek, T.Schreiner, M.Gueorguieva, and C.Ranftler (2006).
Phenol red reduces ROSC mediated cell cycle arrest and apoptosis in human MCF-7 cells.
  J Cell Biochem, 98, 1367-1379.  
16892371 M.D.Kelly, and R.L.Mancera (2006).
Comparative analysis of the surface interaction properties of the binding sites of CDK2, CDK4, and ERK2.
  ChemMedChem, 1, 366-375.  
16407256 M.Otyepka, I.Bártová, Z.Kríz, and J.Koca (2006).
Different mechanisms of CDK5 and CDK2 activation as revealed by CDK5/p25 and CDK2/cyclin A dynamics.
  J Biol Chem, 281, 7271-7281.  
16575928 P.Dobes, M.Otyepka, M.Strnad, and P.Hobza (2006).
Interaction energies for the purine inhibitor roscovitine with cyclin-dependent kinase 2: correlated ab initio quantum-chemical, DFT and empirical calculations.
  Chemistry, 12, 4297-4304.  
16321160 C.Doucet, G.J.Gutierrez, C.Lindon, T.Lorca, G.Lledo, C.Pinset, and O.Coux (2005).
Multiple phosphorylation events control mitotic degradation of the muscle transcription factor Myf5.
  BMC Biochem, 6, 27.  
15778585 D.Autret, A.Bitar, L.Ferrer, A.Lisbona, and M.Bardiès (2005).
Monte Carlo modeling of gamma cameras for I-131 imaging in targeted radiotherapy.
  Cancer Biother Radiopharm, 20, 77-84.  
16262700 D.Stabenow, H.Probst, and M.van Betteraey-Nikoleit (2005).
Cdk2 activity is dispensable for triggering replicon initiation after transient hypoxia in T24 cells.
  FEBS J, 272, 5623-5634.  
16075305 K.A.Rossi, J.A.Markwalder, S.P.Seitz, C.H.Chang, S.Cox, M.D.Boisclair, L.Brizuela, S.L.Brenner, and P.F.Stouten (2005).
Understanding and modulating cyclin-dependent kinase inhibitor specificity: molecular modeling and biochemical evaluation of pyrazolopyrimidinones as CDK2/cyclin A and CDK4/cyclin D1 inhibitors.
  J Comput Aided Mol Des, 19, 111-122.  
16096806 K.K.Manhani, H.A.Arcuri, N.J.da Silveira, H.B.Uchôa, W.F.de Azevedo, and F.Canduri (2005).
Molecular models of protein kinase 6 from Plasmodium falciparum.
  J Mol Model, 12, 42-48.  
15985434 L.Tang, M.H.Li, P.Cao, F.Wang, W.R.Chang, S.Bach, J.Reinhardt, Y.Ferandin, H.Galons, Y.Wan, N.Gray, L.Meijer, T.Jiang, and D.C.Liang (2005).
Crystal structure of pyridoxal kinase in complex with roscovitine and derivatives.
  J Biol Chem, 280, 31220-31229.
PDB codes: 1ygj 1ygk 1yhj
16227297 M.P.Windisch, M.Frese, A.Kaul, M.Trippler, V.Lohmann, and R.Bartenschlager (2005).
Dissecting the interferon-induced inhibition of hepatitis C virus replication by using a novel host cell line.
  J Virol, 79, 13778-13793.  
15759144 N.J.Silveira, H.B.Uchôa, J.H.Pereira, F.Canduri, L.A.Basso, M.S.Palma, D.S.Santos, and W.F.de Azevedo (2005).
Molecular models of protein targets from Mycobacterium tuberculosis.
  J Mol Model, 11, 160-166.  
15663787 N.J.da Silveira, H.A.Arcuri, C.E.Bonalumi, F.P.de Souza, I.M.Mello, P.Rahal, J.R.Pinho, and W.F.de Azevedo (2005).
Molecular models of NS3 protease variants of the Hepatitis C virus.
  BMC Struct Biol, 5, 1.  
16314496 P.K.Pandey, T.S.Udayakumar, X.Lin, D.Sharma, P.S.Shapiro, and J.D.Fondell (2005).
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15975926 S.Bach, M.Knockaert, J.Reinhardt, O.Lozach, S.Schmitt, B.Baratte, M.Koken, S.P.Coburn, L.Tang, T.Jiang, D.C.Liang, H.Galons, J.F.Dierick, L.A.Pinna, F.Meggio, F.Totzke, C.Schächtele, A.S.Lerman, A.Carnero, Y.Wan, N.Gray, and L.Meijer (2005).
Roscovitine targets, protein kinases and pyridoxal kinase.
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16306619 S.Tamrakar, A.J.Kapasi, and D.H.Spector (2005).
Human cytomegalovirus infection induces specific hyperphosphorylation of the carboxyl-terminal domain of the large subunit of RNA polymerase II that is associated with changes in the abundance, activity, and localization of cdk9 and cdk7.
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15818598 X.Li, K.Tanaka, F.Nakatani, T.Matsunobu, R.Sakimura, M.Hanada, T.Okada, T.Nakamura, and Y.Iwamoto (2005).
Transactivation of cyclin E gene by EWS-Fli1 and antitumor effects of cyclin dependent kinase inhibitor on Ewing's family tumor cells.
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15153188 E.Blagoeva, P.I.Dobrev, J.Malbeck, V.Motyka, M.Strnad, J.Hanus, and R.Vanková (2004).
Cytokinin N-glucosylation inhibitors suppress deactivation of exogenous cytokinins in radish, but their effect on active endogenous cytokinins is counteracted by other regulatory mechanisms.
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Retinoid-dependent mRNA expression and poly-(A) contents in bovine oocytes meiotically arrested and/or matured in vitro.
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A three-hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors.
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Crystallization and preliminary X-ray crystallographic analysis of chorismate synthase from Mycobacterium tuberculosis.
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Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick Type C mice.
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15564503 W.Deng, B.Y.Lin, G.Jin, C.G.Wheeler, T.Ma, J.W.Harper, T.R.Broker, and L.T.Chow (2004).
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PPARgamma1 synthesis and adipogenesis in C3H10T1/2 cells depends on S-phase progression, but does not require mitotic clonal expansion.
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PDB codes: 1h1p 1h1q 1h1r 1h1s
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Cyclin-dependent kinases govern formation and maintenance of the nucleolus.
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PDB code: 1flh
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Phosphorylation of RGS9-1 by an endogenous protein kinase in rod outer segments.
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PDB codes: 1j91 1jam
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ATP site-directed competitive and irreversible inhibitors of protein kinases.
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PDB code: 1dm2
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Crystallization, preliminary X-ray analysis and molecular-replacement solution of the carboxy form of haemoglobin I from the fish Brycon cephalus.
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Intra-M phase-promoting factor phosphorylation of cyclin B at the prophase/metaphase transition.
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Crystallization and x-ray diffraction data analysis of human deoxyhaemoglobin A(0) fully stripped of any anions.
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Cdc2 and Cdk2 kinase activated by transforming growth factor-beta1 trigger apoptosis through the phosphorylation of retinoblastoma protein in FaO hepatoma cells.
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Varicella-zoster virus Fc receptor component gI is phosphorylated on its endodomain by a cyclin-dependent kinase.
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Crystal structure of the potent natural product inhibitor balanol in complex with the catalytic subunit of cAMP-dependent protein kinase.
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PDB code: 1bx6
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The development and therapeutic potential of protein kinase inhibitors.
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p35, the neuronal-specific activator of cyclin-dependent kinase 5 (Cdk5) is degraded by the ubiquitin-proteasome pathway.
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c-Myc or cyclin D1 mimics estrogen effects on cyclin E-Cdk2 activation and cell cycle reentry.
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Structural basis of inhibitor selectivity in MAP kinases.
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PDB codes: 1a9u 1bl6 1bl7 1bmk 3erk 4erk
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Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2.
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PDB code: 1aq1
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Direct in vivo inhibition of the nuclear cell cycle cascade in experimental mesangial proliferative glomerulonephritis with Roscovitine, a novel cyclin-dependent kinase antagonist.
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