3e3b › Citations

Structure of human protein kinase CK2 alpha 2 with a potent indazole-derivative inhibitor.

Nakaniwa T, Kinoshita T, Sekiguchi Y, Tada T, Nakanishi I, Kitaura K, Suzuki Y, Ohno H, Hirasawa A, Tsujimoto G
Acta Crystallogr Sect F Struct Biol Cryst Commun 65 75-9 (2009)
Cited: 12 times
EuropePMC logo PMID: 19193990

Abstract

Casein kinase 2 (CK2) is a serine/threonine kinase that functions as a heterotetramer composed of two catalytic subunits (CK2alpha1 or CK2alpha2) and two regulatory subunits (CK2beta). The two isozymes CK2alpha1 and CK2alpha2 play distinguishable roles in healthy subjects and in patients with diseases such as cancer, respectively. In order to develop novel CK2alpha1-selective inhibitors, the crystal structure of human CK2alpha2 (hCK2alpha2) complexed with a potent CK2alpha inhibitor which binds to the active site of hCK2alpha2 was determined and compared with that of human CK2alpha1. While the two isozymes exhibited a high similarity with regard to the active site, the largest structural difference between the isoforms occurred in the beta4-beta5 loop responsible for the CK2alpha-CK2beta interface. The top of the N-terminal segment interacted with the beta4-beta5 loop via a hydrogen bond in hCK2alpha2 but not in hCK2alpha1. Thus, the CK2alpha-CK2beta interface is a likely target candidate for the production of selective CK2alpha1 inhibitors.

Articles - 3e3b mentioned but not cited (3)

  1. Structure of human protein kinase CK2 alpha 2 with a potent indazole-derivative inhibitor. Nakaniwa T, Kinoshita T, Sekiguchi Y, Tada T, Nakanishi I, Kitaura K, Suzuki Y, Ohno H, Hirasawa A, Tsujimoto G. Acta Crystallogr Sect F Struct Biol Cryst Commun 65 75-79 (2009)
  2. Unexpected Binding Mode of a Potent Indeno[1,2-b]indole-Type Inhibitor of Protein Kinase CK2 Revealed by Complex Structures with the Catalytic Subunit CK2α and Its Paralog CK2α'. Hochscherf J, Lindenblatt D, Witulski B, Birus R, Aichele D, Marminon C, Bouaziz Z, Le Borgne M, Jose J, Niefind K. Pharmaceuticals (Basel) 10 E98 (2017)
  3. Crystal structures of human CK2α2 in new crystal forms arising from a subtle difference in salt concentration. Tsuyuguchi M, Nakaniwa T, Kinoshita T. Acta Crystallogr F Struct Biol Commun 74 288-293 (2018)


Reviews citing this publication (3)

  1. Casein kinases as potential therapeutic targets. Cozza G, Pinna LA. Expert Opin Ther Targets 20 319-340 (2016)
  2. How druggable is protein kinase CK2? Cozza G, Bortolato A, Moro S. Med Res Rev 30 419-462 (2010)
  3. Protein Kinase CK2α', More than a Backup of CK2α. Montenarh M, Götz C. Cells 12 2834 (2023)

Articles citing this publication (6)

  1. Structure of the human protein kinase CK2 catalytic subunit CK2α' and interaction thermodynamics with the regulatory subunit CK2β. Bischoff N, Olsen B, Raaf J, Bretner M, Issinger OG, Niefind K. J Mol Biol 407 1-12 (2011)
  2. Enzymatic activity with an incomplete catalytic spine: insights from a comparative structural analysis of human CK2α and its paralogous isoform CK2α'. Bischoff N, Raaf J, Olsen B, Bretner M, Issinger OG, Niefind K. Mol Cell Biochem 356 57-65 (2011)
  3. Evidence for aggregation of protein kinase CK2 in the cell: a novel strategy for studying CK2 holoenzyme interaction by BRET(2). Hübner GM, Larsen JN, Guerra B, Niefind K, Vrecl M, Issinger OG. Mol Cell Biochem 397 285-293 (2014)
  4. Exploring the prominent performance of CX-4945 derivatives as protein kinase CK2 inhibitors by a combined computational study. Wang X, Pan P, Li Y, Li D, Hou T. Mol Biosyst 10 1196-1210 (2014)
  5. Diacritic Binding of an Indenoindole Inhibitor by CK2α Paralogs Explored by a Reliable Path to Atomic Resolution CK2α' Structures. Lindenblatt D, Nickelsen A, Applegate VM, Hochscherf J, Witulski B, Bouaziz Z, Marminon C, Bretner M, Le Borgne M, Jose J, Niefind K. ACS Omega 4 5471-5478 (2019)
  6. Characterization of RAGE and CK2 Expressions in Human Fetal Membranes. Coste K, Bruet S, Chollat-Namy C, Filhol O, Cochet C, Gallot D, Marceau G, Blanchon L, Sapin V, Belville C. Int J Mol Sci 24 4074 (2023)


Quick links