6HMQ
STRUCTURE OF PROTEIN KINASE CK2 CATALYTIC SUBUNIT (ISOFORM CK2ALPHA'; CSNK2A2 GENE PRODUCT) IN COMPLEX WITH THE BENZOTRIAZOLE-TYPE INHIBITOR MB002
Summary for 6HMQ
| Entry DOI | 10.2210/pdb6hmq/pdb |
| Related | 3OFM |
| Descriptor | Casein kinase II subunit alpha', 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, 1,2-ETHANEDIOL, ... (7 entities in total) |
| Functional Keywords | protein kinase ck2, casein kinase 2, catalytic subunit ck2alpha', csnk2a2, transferase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 44209.37 |
| Authors | Niefind, K.,Lindenblatt, D.,Applegate, V.M.,Jose, J.,Le Borgne, M. (deposition date: 2018-09-12, release date: 2019-03-27, Last modification date: 2024-05-15) |
| Primary citation | Lindenblatt, D.,Nickelsen, A.,Applegate, V.M.,Hochscherf, J.,Witulski, B.,Bouaziz, Z.,Marminon, C.,Bretner, M.,Le Borgne, M.,Jose, J.,Niefind, K. Diacritic Binding of an Indenoindole Inhibitor by CK2 alpha Paralogs Explored by a Reliable Path to Atomic Resolution CK2 alpha ' Structures. Acs Omega, 4:5471-5478, 2019 Cited by PubMed Abstract: CK2α and CK2α' are the two isoforms of the catalytic subunit of human protein kinase CK2, an important target for cancer therapy. They have similar, albeit not identical functional and structural properties, and were occasionally reported to be inhibited with distinct efficacies by certain ATP-competitive ligands. Here, we present THN27, an indeno[1,2-]indole derivative, as a further inhibitor with basal isoform selectivity. The selectivity disappears when measured using CK2α/CK2α' complexes with CK2β, the regulatory CK2 subunit. Co-crystal structures of THN27 with CK2α and CK2α' reveal that subtle differences in the conformational variability of the interdomain hinge region are correlated with the observed effect. In the case of CK2α', a crystallographically problematic protein so far, this comparative structural analysis required the development of an experimental strategy that finally enables atomic resolution structure determinations with ab initio phasing of potentially any ATP-competitive CK2 inhibitor and possibly many non-ATP-competitive ligands as well bound to CK2α'. PubMed: 31559376DOI: 10.1021/acsomega.8b03415 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (0.97 Å) |
Structure validation
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