4IB5

Structure of human protein kinase CK2 catalytic subunit in complex with a CK2beta-competitive cyclic peptide

Summary for 4IB5

• Entry DOI: 10.2210/pdb4ib5/pdb
• Related: 1PJK 1jwh 2PVR
• Descriptor: Casein kinase II subunit alpha, CK2beta-derived cyclic peptide, GLYCEROL, ... (5 entities in total)
• Functional Keywords: protein kinase fold, protein phosphorylation, binding of ck2beta, phosphorylation, nucleus, transferase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 126790.20

Authors

Raaf, J.,Guerra, B.,Neundorf, I.,Bopp, B.,Issinger, O.-G.,Jose, J.,Pietsch, M.,Niefind, K. (deposition date: 2012-12-08, release date: 2013-03-20, Last modification date: 2024-10-30)

Primary citation

Raaf, J.,Guerra, B.,Neundorf, I.,Bopp, B.,Issinger, O.G.,Jose, J.,Pietsch, M.,Niefind, K.
First structure of protein kinase CK2 catalytic subunit with an effective CK2 beta-competitive ligand
Acs Chem.Biol., 8:901-907, 2013

PubMed Abstract: The constitutively active Ser/Thr kinase CK2 (casein kinase 2) is used by tumor cells to acquire apoptosis resistance. CK2 exists as a heterotetrameric holoenzyme with two catalytic chains (CK2α) attached to a dimer of noncatalytic subunits (CK2β). A druggable cavity at the CK2β interface of CK2α allows the design of small molecules disturbing the CK2α/CK2β interaction and thus affecting activity, stability, and substrate specificity. We describe here the first structure of CK2α with an effective CK2β-competitive compound, namely, a 13-meric cyclic peptide derived from the C-terminal CK2β segment. Some well-ordered water molecules not visible in CK2 holoenzyme structures were detected at the interface. Driven mainly by enthalpy, the peptide binds with submicromolar affinity to CK2α, stimulates its catalytic activity, and reduces effectively the CK2α/CK2β affinity. The results provide a thermodynamic and structural rationalization of the peptide's CK2β-competitive functionality and pave thus the way to a peptidomimetic drug addressing the CK2α/CK2β interaction.

PubMed: 23474121
DOI: 10.1021/cb3007133

Experimental method

X-RAY DIFFRACTION (2.2 Å)