4ib5

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

Structural highlights 4ib5 is a 7 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CSK21_HUMAN Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Publication Abstract from PubMed 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 (CK2alpha) attached to a dimer of noncatalytic subunits (CK2beta). A druggable cavity at the CK2beta interface of CK2alpha allows the design of small molecules disturbing the CK2alpha/CK2beta interaction and thus affecting activity, stability, and substrate specificity. We describe here the first structure of CK2alpha with an effective CK2beta-competitive compound, namely, a 13-meric cyclic peptide derived from the C-terminal CK2beta 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 CK2alpha, stimulates its catalytic activity, and reduces effectively the CK2alpha/CK2beta affinity. The results provide a thermodynamic and structural rationalization of the peptide's CK2beta-competitive functionality and pave thus the way to a peptidomimetic drug addressing the CK2alpha/CK2beta interaction. First Structure of Protein Kinase CK2 Catalytic Subunit with an Effective CK2beta-Competitive Ligand.,Raaf J, Guerra B, Neundorf I, Bopp B, Issinger OG, Jose J, Pietsch M, Niefind K ACS Chem Biol. 2013 Mar 18. PMID:23474121 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Casein kinase 3D structures

spinqualitylabelsall models 4ib5, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image