4RLK

Crystal structure of Z. mays CK2alpha in complex with the ATP-competitive inhibitor 4-[(E)-(fluoren-9-ylidenehydrazinylidene)-methyl] benzoate

Summary for 4RLK

• Entry DOI: 10.2210/pdb4rlk/pdb
• Related: 4RLL
• Descriptor: Casein kinase II subunit alpha, GLYCEROL, ACETATE ION, ... (5 entities in total)
• Functional Keywords: transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Zea mays (maize)
• Total number of polymer chains: 1
• Total formula weight: 40011.88

Authors

Guerra, B.,Rasmussen, T.D.L.,Schnitzler, A.,Jensen, H.H.,Boldyreff, B.S.,Miyata, Y.,Marcussen, N.,Niefind, K.,Issinger, O.G. (deposition date: 2014-10-17, release date: 2014-12-17, Last modification date: 2023-09-20)

Primary citation

Guerra, B.,Rasmussen, T.D.,Schnitzler, A.,Jensen, H.H.,Boldyreff, B.S.,Miyata, Y.,Marcussen, N.,Niefind, K.,Issinger, O.G.
Protein kinase CK2 inhibition is associated with the destabilization of HIF-1 alpha in human cancer cells.
Cancer Lett, 356:751-761, 2015

PubMed Abstract: Screening for protein kinase CK2 inhibitors of the structural diversity compound library (DTP NCI/NIH) led to the discovery of 4-[(E)-(fluoren-9-ylidenehydrazinylidene)-methyl]benzoic acid (E9). E9 induces apoptotic cell death in various cancer cell lines and upon hypoxia, the compound suppresses CK2-catalyzed HSP90/Cdc37 phosphorylation and induces HIF-1α degradation. Furthermore, E9 exerts a strong anti-tumour activity by inducing necrosis in murine xenograft models underlining its potential to be used for cancer treatment in future clinical studies. Crystal structure analysis of human and maize CK2α in complex with E9 reveals unique binding properties of the inhibitor to the enzyme, accounting for its affinity and selectivity.

PubMed: 25449433
DOI: 10.1016/j.canlet.2014.10.026

Experimental method

X-RAY DIFFRACTION (1.24 Å)