3RPS

Structure of human CK2alpha in complex with the ATP-competitive inhibitor 3-(4,5,6,7-tetrabromo-1H-benzotriazol-1-yl)propan-1-ol

Summary for 3RPS

• Entry DOI: 10.2210/pdb3rps/pdb
• Related: 1JWH 3OFM 3RP0
• Descriptor: Casein kinase II subunit alpha, 3-(4,5,6,7-tetrabromo-1H-benzotriazol-1-yl)propan-1-ol, SULFATE ION, ... (5 entities in total)
• Functional Keywords: eukaryotic protein kinase fold, atp ck2beta, phosphorylation, cytoplasm nucleus, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 80960.21

Authors

Bischoff, N.,Raaf, J.,Olsen, B.,Bretner, M.,Issinger, O.-G.,Niefind, K. (deposition date: 2011-04-27, release date: 2011-06-08, Last modification date: 2024-02-28)

Primary citation

Bischoff, N.,Raaf, J.,Olsen, B.,Bretner, M.,Issinger, O.G.,Niefind, K.
Enzymatic activity with an incomplete catalytic spine - insights from a comparative structural analysis of human CK2alpha and its paralogous isoform CK2alpha'
Mol.Cell.Biochem., 356:57-65, 2011

PubMed Abstract: Eukaryotic protein kinases are fundamental factors for cellular regulation and therefore subject of strict control mechanisms. For full activity a kinase molecule must be penetrated by two stacks of hydrophobic residues, the regulatory and the catalytic spine that are normally well conserved among active protein kinases. We apply this novel spine concept here on CK2α, the catalytic subunit of protein kinase CK2. Homo sapiens disposes of two paralog isoforms of CK2α (hsCK2α and hsCK2α'). We describe two new structures of hsCK2α constructs one of which in complex with the ATP-analog adenylyl imidodiphosphate and the other with the ATP-competitive inhibitor 3-(4,5,6,7-tetrabromo-1H-benzotriazol-1-yl)propan-1-ol. The former is the first hsCK2α structure with a well defined cosubstrate/magnesium complex and the second with an open β4/β5-loop. Comparisons of these structures with existing CK2α/CK2α' and cAMP-dependent protein kinase (PKA) structures reveal: in hsCK2α' an open conformation of the interdomain hinge/helix αD region that is critical for ATP-binding is found corresponding to an incomplete catalytic spine. In contrast hsCK2α often adopts the canonical, PKA-like version of the catalytic spine which correlates with a closed conformation of the hinge region. HsCK2α can switch to the incomplete, non-canonical, hsCK2α'-like state of the catalytic spine, but this transition apparently depends on binding of either ATP or of the regulatory subunit CK2β. Thus, ATP looks like an activator of hsCK2α rather than a pure cosubstrate.

PubMed: 21739153
DOI: 10.1007/s11010-011-0948-5

Experimental method

X-RAY DIFFRACTION (2.3 Å)