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PDBsum entry 1aq1

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Protein kinase PDB id
1aq1
Jmol
Contents
Protein chain
277 a.a. *
Ligands
STU
Waters ×125
* Residue conservation analysis
PDB id:
1aq1
Name: Protein kinase
Title: Human cyclin dependent kinase 2 complexed with the inhibitor staurosporine
Structure: Cyclin-dependent protein kinase 2. Chain: a. Synonym: cdk2. Engineered: yes. Other_details: complex with cyclin a or cyclin e
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: sf9. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108. Expression_system_cell_line: sf9.
Resolution:
2.00Å     R-factor:   0.220     R-free:   0.260
Authors: J.A.Endicott,M.E.M.Noble,L.N.Johnson,A.Lawrie,P.Tunnah, N.R.Brown
Key ref: A.M.Lawrie et al. (1997). Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2. Nat Struct Biol, 4, 796-801. PubMed id: 9334743
Date:
05-Aug-97     Release date:   12-Nov-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P24941  (CDK2_HUMAN) -  Cyclin-dependent kinase 2
Seq:
Struc:
298 a.a.
277 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   28 terms 
  Biochemical function     nucleotide binding     12 terms  

 

 
    reference    
 
 
Nat Struct Biol 4:796-801 (1997)
PubMed id: 9334743  
 
 
Protein kinase inhibition by staurosporine revealed in details of the molecular interaction with CDK2.
A.M.Lawrie, M.E.Noble, P.Tunnah, N.R.Brown, L.N.Johnson, J.A.Endicott.
 
  ABSTRACT  
 
Staurosporine exhibits nanomolar IC50 values against a wide range of protein kinases. The structure of a CDK2 staurosporine complex explains the tight binding of this inhibitor, and suggests features to be exploited in the design of specific inhibitors of CDKs.
 

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.  
19674907 C.D.Shomin, S.C.Meyer, and I.Ghosh (2009).
Staurosporine tethered peptide ligands that target cAMP-dependent protein kinase (PKA): optimization and selectivity profiling.
  Bioorg Med Chem, 17, 6196-6202.  
19489734 M.K.Tarrant, and P.A.Cole (2009).
The chemical biology of protein phosphorylation.
  Annu Rev Biochem, 78, 797-825.  
19008858 C.Mieczkowski, A.T.Iavarone, and T.Alber (2008).
Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor Ser/Thr kinase.
  EMBO J, 27, 3186-3197.
PDB codes: 3f61 3f69
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.  
17937911 G.Bunkoczi, E.Salah, P.Filippakopoulos, O.Fedorov, S.Müller, F.Sobott, S.A.Parker, H.Zhang, W.Min, B.E.Turk, and S.Knapp (2007).
Structural and functional characterization of the human protein kinase ASK1.
  Structure, 15, 1215-1226.
PDB code: 2clq
17965187 M.Ikuta, M.Kornienko, N.Byrne, J.C.Reid, S.Mizuarai, H.Kotani, and S.K.Munshi (2007).
Crystal structures of the N-terminal kinase domain of human RSK1 bound to three different ligands: Implications for the design of RSK1 specific inhibitors.
  Protein Sci, 16, 2626-2635.
PDB codes: 2z7q 2z7r 2z7s
17406720 N.Pagano, J.Maksimoska, H.Bregman, D.S.Williams, R.D.Webster, F.Xue, and E.Meggers (2007).
Ruthenium half-sandwich complexes as protein kinase inhibitors: derivatization of the pyridocarbazole pharmacophore ligand.
  Org Biomol Chem, 5, 1218-1227.
PDB code: 2oi4
17119643 C.Sánchez, C.Méndez, and J.A.Salas (2006).
Indolocarbazole natural products: occurrence, biosynthesis, and biological activity.
  Nat Prod Rep, 23, 1007-1045.  
16381041 J.E.Debreczeni, A.N.Bullock, G.E.Atilla, D.S.Williams, H.Bregman, S.Knapp, and E.Meggers (2006).
Ruthenium half-sandwich complexes bound to protein kinase Pim-1.
  Angew Chem Int Ed Engl, 45, 1580-1585.  
16584130 J.Sridhar, N.Akula, and N.Pattabiraman (2006).
Selectivity and potency of cyclin-dependent kinase inhibitors.
  AAPS J, 8, E204-E221.  
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.  
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.  
16917500 R.Jauch, M.K.Cho, S.Jäkel, C.Netter, K.Schreiter, B.Aicher, M.Zweckstetter, H.Jäckle, and M.C.Wahl (2006).
Mitogen-activated protein kinases interacting kinases are autoinhibited by a reprogrammed activation segment.
  EMBO J, 25, 4020-4032.
PDB codes: 2hw6 2hw7
16622124 S.Yaguchi, Y.Fukui, I.Koshimizu, H.Yoshimi, T.Matsuno, H.Gouda, S.Hirono, K.Yamazaki, and T.Yamori (2006).
Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor.
  J Natl Cancer Inst, 98, 545-556.  
16761096 T.J.Zhou, L.G.Sun, Y.Gao, and E.J.Goldsmith (2006).
Crystal structure of the MAP3K TAO2 kinase domain bound by an inhibitor staurosporine.
  Acta Biochim Biophys Sin (Shanghai), 38, 385-392.
PDB code: 2gcd
16186927 D.Moffat, C.J.Nichols, D.A.Riley, and N.S.Simpkins (2005).
The synthesis of bioactive indolocarbazoles related to K-252a.
  Org Biomol Chem, 3, 2953-2975.  
15742314 D.S.Williams, G.E.Atilla, H.Bregman, A.Arzoumanian, P.S.Klein, and E.Meggers (2005).
Switching on a signaling pathway with an organoruthenium complex.
  Angew Chem Int Ed Engl, 44, 1984-1987.  
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.  
16075446 S.Barrett, S.Bartlett, A.Bolt, A.Ironmonger, C.Joce, A.Nelson, and T.Woodhall (2005).
Configurational stability of bisindolylmaleimide cyclophanes: from conformers to the first configurationally stable, atropisomeric bisindolylmaleimides.
  Chemistry, 11, 6277-6285.  
15292186 L.Jin, S.Pluskey, E.C.Petrella, S.M.Cantin, J.C.Gorga, M.J.Rynkiewicz, P.Pandey, J.E.Strickler, R.E.Babine, D.T.Weaver, and K.J.Seidl (2004).
The three-dimensional structure of the ZAP-70 kinase domain in complex with staurosporine: implications for the design of selective inhibitors.
  J Biol Chem, 279, 42818-42825.
PDB code: 1u59
14996846 M.Gassel, C.B.Breitenlechner, N.König, R.Huber, R.A.Engh, and D.Bossemeyer (2004).
The protein kinase C inhibitor bisindolyl maleimide 2 binds with reversed orientations to different conformations of protein kinase A.
  J Biol Chem, 279, 23679-23690.
PDB code: 1szm
15507431 S.Atwell, J.M.Adams, J.Badger, M.D.Buchanan, I.K.Feil, K.J.Froning, X.Gao, J.Hendle, K.Keegan, B.C.Leon, H.J.Müller-Dieckmann, V.L.Nienaber, B.W.Noland, K.Post, K.R.Rajashankar, A.Ramos, M.Russell, S.K.Burley, and S.G.Buchanan (2004).
A novel mode of Gleevec binding is revealed by the structure of spleen tyrosine kinase.
  J Biol Chem, 279, 55827-55832.
PDB codes: 1xba 1xbb 1xbc
15048820 Z.Kríz, M.Otyepka, I.Bártová, and J.Koca (2004).
Analysis of CDK2 active-site hydration: a method to design new inhibitors.
  Proteins, 55, 258-274.  
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
14559966 N.Schiering, S.Knapp, M.Marconi, M.M.Flocco, J.Cui, R.Perego, L.Rusconi, and C.Cristiani (2003).
Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a.
  Proc Natl Acad Sci U S A, 100, 12654-12659.
PDB codes: 1r0p 1r1w
12789688 T.Honma (2003).
Recent advances in de novo design strategy for practical lead identification.
  Med Res Rev, 23, 606-632.  
12244092 B.Zhao, M.J.Bower, P.J.McDevitt, H.Zhao, S.T.Davis, K.O.Johanson, S.M.Green, N.O.Concha, and B.B.Zhou (2002).
Structural basis for Chk1 inhibition by UCN-01.
  J Biol Chem, 277, 46609-46615.
PDB codes: 1nvq 1nvr 1nvs
12191602 D.Fabbro, S.Ruetz, E.Buchdunger, S.W.Cowan-Jacob, G.Fendrich, J.Liebetanz, J.Mestan, T.O'Reilly, P.Traxler, B.Chaudhuri, H.Fretz, J.Zimmermann, T.Meyer, G.Caravatti, P.Furet, and P.W.Manley (2002).
Protein kinases as targets for anticancer agents: from inhibitors to useful drugs.
  Pharmacol Ther, 93, 79-98.  
12191604 L.N.Johnson, E.De Moliner, N.R.Brown, H.Song, D.Barford, J.A.Endicott, and M.E.Noble (2002).
Structural studies with inhibitors of the cell cycle regulatory kinase cyclin-dependent protein kinase 2.
  Pharmacol Ther, 93, 113-124.  
12237154 M.Knockaert, P.Greengard, and L.Meijer (2002).
Pharmacological inhibitors of cyclin-dependent kinases.
  Trends Pharmacol Sci, 23, 417-425.  
12191603 R.A.Engh, and D.Bossemeyer (2002).
Structural aspects of protein kinase control-role of conformational flexibility.
  Pharmacol Ther, 93, 99.  
12191605 T.G.Davies, D.J.Pratt, J.A.Endicott, L.N.Johnson, and M.E.Noble (2002).
Structure-based design of cyclin-dependent kinase inhibitors.
  Pharmacol Ther, 93, 125-133.  
11306297 A.C.Bishop, O.Buzko, and K.M.Shokat (2001).
Magic bullets for protein kinases.
  Trends Cell Biol, 11, 167-172.  
11327879 G.Conseil, J.M.Perez-Victoria, J.M.Jault, F.Gamarro, A.Goffeau, J.Hofmann, and A.Di Pietro (2001).
Protein kinase C effectors bind to multidrug ABC transporters and inhibit their activity.
  Biochemistry, 40, 2564-2571.  
11090628 E.H.Walker, M.E.Pacold, O.Perisic, L.Stephens, P.T.Hawkins, M.P.Wymann, and R.L.Williams (2000).
Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine.
  Mol Cell, 6, 909-919.
PDB codes: 1e7u 1e7v 1e8w 1e8x 1e8y 1e8z 1e90
11076534 J.N.Adkins, and K.J.Lumb (2000).
Stoichiometry of cyclin A-cyclin-dependent kinase 2 inhibition by p21Cip1/Waf1.
  Biochemistry, 39, 13925-13930.  
10662688 L.Meijer, A.M.Thunnissen, A.W.White, M.Garnier, M.Nikolic, L.H.Tsai, J.Walter, K.E.Cleverley, P.C.Salinas, Y.Z.Wu, J.Biernat, E.M.Mandelkow, S.H.Kim, and G.R.Pettit (2000).
Inhibition of cyclin-dependent kinases, GSK-3beta and CK1 by hymenialdisine, a marine sponge constituent.
  Chem Biol, 7, 51-63.
PDB code: 1dm2
  10564281 H.Bastians, L.M.Topper, G.L.Gorbsky, and J.V.Ruderman (1999).
Cell cycle-regulated proteolysis of mitotic target proteins.
  Mol Biol Cell, 10, 3927-3941.  
10454194 J.M.Sowadski, L.F.Epstein, L.Lankiewicz, and R.Karlsson (1999).
Conformational diversity of catalytic cores of protein kinases.
  Pharmacol Ther, 82, 157-164.  
10454204 M.E.Noble, and J.A.Endicott (1999).
Chemical inhibitors of cyclin-dependent kinases: insights into design from X-ray crystallographic studies.
  Pharmacol Ther, 82, 269-278.  
10092646 P.Sharma, P.J.Steinbach, M.Sharma, N.D.Amin, J.J.Barchi, and H.C.Pant (1999).
Identification of substrate binding site of cyclin-dependent kinase 5.
  J Biol Chem, 274, 9600-9606.  
10454197 P.Traxler, and P.Furet (1999).
Strategies toward the design of novel and selective protein tyrosine kinase inhibitors.
  Pharmacol Ther, 82, 195-206.  
10404594 X.Zhu, J.L.Kim, J.R.Newcomb, P.E.Rose, D.R.Stover, L.M.Toledo, H.Zhao, and K.A.Morgenstern (1999).
Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors.
  Structure, 7, 651-661.
PDB codes: 1qpc 1qpd 1qpe 1qpj
9756886 A.K.Konstantinidis, R.Radhakrishnan, F.Gu, R.N.Rao, and W.K.Yeh (1998).
Purification, characterization, and kinetic mechanism of cyclin D1. CDK4, a major target for cell cycle regulation.
  J Biol Chem, 273, 26506-26515.  
9837816 H.Mehenni, C.Gehrig, J.Nezu, A.Oku, M.Shimane, C.Rossier, N.Guex, J.L.Blouin, H.S.Scott, and S.E.Antonarakis (1998).
Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity.
  Am J Hum Genet, 63, 1641-1650.  
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.