PDBsum entry 1m2p

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Transferase PDB id
Protein chain
325 a.a. *
Waters ×177
* Residue conservation analysis
PDB id:
Name: Transferase
Title: Crystal structure of 1,8-di-hydroxy-4-nitro- anthraquinone/ck2 kinase complex
Structure: Casein kinase ii, alpha chain. Chain: a. Fragment: catlytic subunit. Synonym: ckii. Engineered: yes
Source: Zea mays. Organism_taxid: 4577. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
2.00Å     R-factor:   0.223     R-free:   0.243
Authors: E.De Moliner,S.Moro,S.Sarno,G.Zagotto,G.Zanotti,L.A.Pinna, R.Battistutta
Key ref:
E.De Moliner et al. (2003). Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight. J Biol Chem, 278, 1831-1836. PubMed id: 12419810 DOI: 10.1074/jbc.M209367200
25-Jun-02     Release date:   17-Jun-03    
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Protein chain
Pfam   ArchSchema ?
P28523  (CSK2A_MAIZE) -  Casein kinase II subunit alpha
332 a.a.
325 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Non-specific serine/threonine protein 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!
  Biological process     phosphorylation   2 terms 
  Biochemical function     nucleotide binding     7 terms  


DOI no: 10.1074/jbc.M209367200 J Biol Chem 278:1831-1836 (2003)
PubMed id: 12419810  
Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight.
E.De Moliner, S.Moro, S.Sarno, G.Zagotto, G.Zanotti, L.A.Pinna, R.Battistutta.
Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition.
  Selected figure(s)  
Figure 2.
Fig. 2. Overview of CK2 three-dimensional folding. The ribbon diagram of CK2 in complex with MNA (in ball-and-stick) bound in the ATP binding site between the N- and the C-terminal lobes is shown (gray). The location of the inhibitor DAA is also shown (ball-and-stick in black). On the top right are shown the two different positions of the loop 102-108 in the case of the MNA complex (gray) and DAA (or MNX) complex (black) that correspond to a long b-cell axis (around 59.5 Å) and a short one (around 52.2 Å), respectively.
Figure 4.
Fig. 4. Polar interactions (dotted lines) of MNA , MNX, and DAA when bound to CK2. Distances are reported in angstroms. In the DAA scheme, interactions between ATP and residues Glu-114 and Val-116 are reported for comparison (21).
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 1831-1836) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19526464 G.Cozza, A.Bortolato, and S.Moro (2010).
How druggable is protein kinase CK2?
  Med Res Rev, 30, 419-462.  
19821123 N.Zhang, and R.Zhong (2010).
Structural basis for decreased affinity of Emodin binding to Val66-mutated human CK2 alpha as determined by molecular dynamics.
  J Mol Model, 16, 771-780.  
  19193990 T.Nakaniwa, T.Kinoshita, Y.Sekiguchi, T.Tada, I.Nakanishi, K.Kitaura, Y.Suzuki, H.Ohno, A.Hirasawa, and G.Tsujimoto (2009).
Structure of human protein kinase CK2 alpha 2 with a potent indazole-derivative inhibitor.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 75-79.
PDB code: 3e3b
18704226 S.Sarno, and L.A.Pinna (2008).
Protein kinase CK2 as a druggable target.
  Mol Biosyst, 4, 889-894.  
17486073 G.Di Maira, F.Brustolon, J.Bertacchini, K.Tosoni, S.Marmiroli, L.A.Pinna, and M.Ruzzene (2007).
Pharmacological inhibition of protein kinase CK2 reverts the multidrug resistance phenotype of a CEM cell line characterized by high CK2 level.
  Oncogene, 26, 6915-6926.  
17133643 M.A.Pagano, G.Poletto, G.Di Maira, G.Cozza, M.Ruzzene, S.Sarno, J.Bain, M.Elliott, S.Moro, G.Zagotto, F.Meggio, and L.A.Pinna (2007).
Tetrabromocinnamic acid (TBCA) and related compounds represent a new class of specific protein kinase CK2 inhibitors.
  Chembiochem, 8, 129-139.  
17768728 R.Battistutta, M.Mazzorana, L.Cendron, A.Bortolato, S.Sarno, Z.Kazimierczuk, G.Zanotti, S.Moro, and L.A.Pinna (2007).
The ATP-binding site of protein kinase CK2 holds a positive electrostatic area and conserved water molecules.
  Chembiochem, 8, 1804-1809.
PDB codes: 2oxd 2oxx 2oxy
17676727 X.Hu, G.Prehna, and C.E.Stebbins (2007).
Targeting plague virulence factors: a combined machine learning method and multiple conformational virtual screening for the discovery of Yersinia protein kinase A inhibitors.
  J Med Chem, 50, 3980-3983.  
16298300 R.Battistutta, M.Mazzorana, S.Sarno, Z.Kazimierczuk, G.Zanotti, and L.A.Pinna (2005).
Inspecting the structure-activity relationship of protein kinase CK2 inhibitors derived from tetrabromo-benzimidazole.
  Chem Biol, 12, 1211-1219.
PDB codes: 1zoe 1zog 1zoh
16335530 S.Sarno, M.Ruzzene, P.Frascella, M.A.Pagano, F.Meggio, A.Zambon, M.Mazzorana, G.Di Maira, V.Lucchini, and L.A.Pinna (2005).
Development and exploitation of CK2 inhibitors.
  Mol Cell Biochem, 274, 69-76.  
14596595 B.E.Aubol, B.Nolen, J.Shaffer, G.Ghosh, and J.A.Adams (2003).
Novel destabilization of nucleotide binding by the gamma phosphate of ATP in the yeast SR protein kinase Sky1p.
  Biochemistry, 42, 12813-12820.  
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 code is shown on the right.