3OWK
Human CK2 catalytic domain in complex with a benzopyridoindole derivative inhibitor
Summary for 3OWK
| Entry DOI | 10.2210/pdb3owk/pdb |
| Related | 3MB6 3MB7 3OWJ 3OWL |
| Descriptor | CSNK2A1 protein, 7-chloro-10-methyl-11H-benzo[g]pyrido[4,3-b]indol-3-ol, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | serine/threonine-protein kinase, ck2, inhibitor, benzopyridoindole, ellipticine, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 40221.14 |
| Authors | Reiser, J.-B.,Prudent, R.,Cochet, C. (deposition date: 2010-09-20, release date: 2010-12-15, Last modification date: 2024-02-21) |
| Primary citation | Prudent, R.,Moucadel, V.,Nguyen, C.H.,Barette, C.,Schmidt, F.,Florent, J.C.,Lafanechere, L.,Sautel, C.F.,Duchemin-Pelletier, E.,Spreux, E.,Filhol, O.,Reiser, J.B.,Cochet, C. Antitumor activity of pyridocarbazole and benzopyridoindole derivatives that inhibit protein kinase CK2. Cancer Res., 70:9865-9874, 2010 Cited by PubMed Abstract: The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison that is used in ovarian and breast cancer treatment. In this study, we report the identification of ellipticine derivatives and their tetracyclic angular benzopyridoindole analogues as novel ATP-competitive inhibitors of the protein kinase CK2. In vitro and in vivo assays showed that these compounds have a good pharmacologic profile, causing a marked inhibition of CK2 activity associated with cell cycle arrest and apoptosis in human cancer cells. Further, in vivo assays demonstrate antitumor activity in a mouse xenograft model of human glioblastoma. Finally, crystal structures of CK2-inhibitor complex provide structural insights on the molecular basis of CK2 inhibition. Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters. PubMed: 21118972DOI: 10.1158/0008-5472.CAN-10-0917 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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