Bischoff, Nils, Raaf, Jennifer, Olsen, Birgitte, Bretner, Maria ORCID: 0000-0002-9643-0843, Issinger, Olaf-Georg and Niefind, Karsten ORCID: 0000-0002-0183-6315 (2011). Enzymatic activity with an incomplete catalytic spine: insights from a comparative structural analysis of human CK2 alpha and its paralogous isoform CK2 alpha'. Mol. Cell. Biochem., 356 (1-2). S. 57 - 66. DORDRECHT: SPRINGER. ISSN 1573-4919

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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 CK2 alpha, the catalytic subunit of protein kinase CK2. Homo sapiens disposes of two paralog isoforms of CK2 alpha (hsCK2 alpha and hsCK2 alpha'). We describe two new structures of hsCK2 alpha 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 hsCK2 alpha structure with a well defined cosubstrate/magnesium complex and the second with an open beta 4/beta 5-loop. Comparisons of these structures with existing CK2 alpha/CK2 alpha' and cAMP-dependent protein kinase (PKA) structures reveal: in hsCK2 alpha' an open conformation of the interdomain hinge/helix alpha D region that is critical for ATP-binding is found corresponding to an incomplete catalytic spine. In contrast hsCK2 alpha often adopts the canonical, PKA-like version of the catalytic spine which correlates with a closed conformation of the hinge region. HsCK2 alpha can switch to the incomplete, non-canonical, hsCK2 alpha'-like state of the catalytic spine, but this transition apparently depends on binding of either ATP or of the regulatory subunit CK2 beta. Thus, ATP looks like an activator of hsCK2 alpha rather than a pure cosubstrate.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bischoff, NilsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raaf, JenniferUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olsen, BirgitteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bretner, MariaUNSPECIFIEDorcid.org/0000-0002-9643-0843UNSPECIFIED
Issinger, Olaf-GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Niefind, KarstenUNSPECIFIEDorcid.org/0000-0002-0183-6315UNSPECIFIED
URN: urn:nbn:de:hbz:38-487892
DOI: 10.1007/s11010-011-0948-5
Journal or Publication Title: Mol. Cell. Biochem.
Volume: 356
Number: 1-2
Page Range: S. 57 - 66
Date: 2011
Publisher: SPRINGER
Place of Publication: DORDRECHT
ISSN: 1573-4919
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PROTEIN-KINASE CK2; CRYSTAL-STRUCTURE; CONFORMATIONAL PLASTICITY; SUBSTRATE RECOGNITION; SUBUNIT; ATP; MUTANT; DOMAIN; POCKET; SITEMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/48789

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