scholarly journals Site-Directed Mutagenesis in the Research of Protein Kinases - The Case of Protein Kinase CK2

10.5772/54873 ◽  
2013 ◽  
Author(s):  
Ewa Sajnaga ◽  
Ryszard Szyszka ◽  
Konrad Kubinski
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Protein Kinase Ck2 ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Kinase Ck2

scholarly journals Different Susceptibility of Protein Kinases to Staurosporine Inhibition. Kinetic Studies and Molecular Bases for the Resistance of Protein Kinase CK2

1995 ◽  
Vol 234 (1) ◽  
pp. 317-322 ◽  
Author(s):  
Flavio Meggio ◽  
Arianna Donella Deana ◽  
Maria Ruzzene ◽  
Anna M. Brunati ◽  
Luca Cesaro ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Protein Kinase Ck2 ◽  
Kinetic Studies ◽  
Inhibition Kinetic ◽  
Molecular Bases ◽  
Kinase Ck2

scholarly journals Structure-based design of small peptide inhibitors of protein kinase CK2 subunit interaction

2007 ◽  
Vol 408 (3) ◽  
pp. 363-373 ◽  
Author(s):  
Béatrice Laudet ◽  
Caroline Barette ◽  
Vincent Dulery ◽  
Olivier Renaudet ◽  
Pascal Dumy ◽  
...  
Keyword(s):  
Amino Acids ◽  
Protein Kinase ◽  
Protein Kinase Ck2 ◽  
Peptide Inhibitors ◽  
Fluorescent Imaging ◽  
Site Directed Mutagenesis ◽  
Small Peptide ◽  
Double Mutation ◽  
Kinase Ck2

X-ray crystallography studies, as well as live-cell fluorescent imaging, have recently challenged the traditional view of protein kinase CK2. Unbalanced expression of catalytic and regulatory CK2 subunits has been observed in a variety of tissues and tumours. Thus the potential intersubunit flexibility suggested by these studies raises the likely prospect that the CK2 holoenzyme complex is subject to disassembly and reassembly. In the present paper, we show evidence for the reversible multimeric organization of the CK2 holoenzyme complex in vitro. We used a combination of site-directed mutagenesis, binding experiments and functional assays to show that, both in vitro and in vivo, only a small set of primary hydrophobic residues of CK2β which contacts at the centre of the CK2α/CK2β interface dominates affinity. The results indicate that a double mutation in CK2β of amino acids Tyr188 and Phe190, which are complementary and fill up a hydrophobic pocket of CK2α, is the most disruptive to CK2α binding both in vitro and in living cells. Further characterization of hotspots in a cluster of hydrophobic amino acids centred around Tyr188–Phe190 led us to the structure-based design of small-peptide inhibitors. One conformationally constrained 11-mer peptide (Pc) represents a unique CK2β-based small molecule that was particularly efficient (i) to antagonize the interaction between the CK2 subunits, (ii) to inhibit the assembly of the CK2 holoenzyme complex, and (iii) to strongly affect its substrate preference.

scholarly journals Quinalizarin as a potent, selective and cell-permeable inhibitor of protein kinase CK2

2009 ◽  
Vol 421 (3) ◽  
pp. 387-395 ◽  
Author(s):  
Giorgio Cozza ◽  
Marco Mazzorana ◽  
Elena Papinutto ◽  
Jenny Bain ◽  
Matthew Elliott ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Protein Kinase Ck2 ◽  
Integration Site ◽  
Jurkat Cells ◽  
Mitogen Activated Protein Kinase ◽  
Leukaemia Virus ◽  
Kinase Ck2 ◽  
Ck2 Inhibitors ◽  
Ck2 Inhibitor

Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a moderately potent and poorly selective inhibitor of protein kinase CK2, one of the most pleiotropic serine/threonine protein kinases, implicated in neoplasia and in other global diseases. By virtual screening of the MMS (Molecular Modeling Section) database, we have now identified quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) as an inhibitor of CK2 that is more potent and selective than emodin. CK2 inhibition by quinalizarin is competitive with respect to ATP, with a Ki value of approx. 50 nM. Tested at 1 μM concentration on a panel of 75 protein kinases, quinalizarin drastically inhibits only CK2, with a promiscuity score (11.1), which is the lowest ever reported so far for a CK2 inhibitor. Especially remarkable is the ability of quinalizarin to discriminate between CK2 and a number of kinases, notably DYRK1a (dual-specificity tyrosine-phosphorylated and -regulated kinase), PIM (provirus integration site for Moloney murine leukaemia virus) 1, 2 and 3, HIPK2 (homeodomain-interacting protein kinase-2), MNK1 [MAPK (mitogen-activated protein kinase)-interacting kinase 1], ERK8 (extracellular-signal-regulated kinase 8) and PKD1 (protein kinase D 1), which conversely tend to be inhibited as drastically as CK2 by commercially available CK2 inhibitors. The determination of the crystal structure of a complex between quinalizarin and CK2α subunit highlights the relevance of polar interactions in stabilizing the binding, an unusual characteristic for a CK2 inhibitor, and disclose other structural features which may account for the narrow selectivity of this compound. Tested on Jurkat cells, quinalizarin proved able to inhibit endogenous CK2 and to induce apoptosis more efficiently than the commonly used CK2 inhibitors TBB (4,5,6,7-tetrabromo-1H-benzotriazole) and DMAT (2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole).

scholarly journals The catalytic subunit of protein kinase CK2 phosphorylates in vitro the movement protein of Tomato mosaic virus

2003 ◽  
Vol 84 (2) ◽  
pp. 497-505 ◽  
Author(s):  
Yasuhiko Matsushita ◽  
Mayumi Ohshima ◽  
Kuniaki Yoshioka ◽  
Masamichi Nishiguchi ◽  
Hiroshi Nyunoya
Keyword(s):  
Protein Kinase ◽  
Mosaic Virus ◽  
Protein Kinase Ck2 ◽  
Movement Protein ◽  
Catalytic Subunit ◽  
Tomato Mosaic Virus ◽  
Kinase Ck2
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