6spx

Structure of protein kinase CK2 catalytic subunit in complex with the CK2beta-competitive bisubstrate inhibitor ARC1502

spinqualitylabelsall models 6spx, resolution 1.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6spx is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.994Å Ligands: 9AB, DAS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Protein kinase CK2, a heterotetrameric holoenzyme composed of two catalytic chains (CK2alpha) attached to a homodimer of regulatory subunits (CK2beta), is a target for drug development for cancer therapy. Here, we describe the tetraiodobenzimidazole derivative ARC-3140, a bisubstrate inhibitor addressing the ATP site and the substrate-binding site of CK2 with extraordinary affinity (Ki = 84 pM). In a crystal structure of ARC-3140 in complex with CK2alpha, three copies of the inhibitor are visible, one of them at the CK2beta interface of CK2alpha. Subsequent interaction studies based on microscale thermophoresis and fluorescence anisotropy changes revealed a significant impact of ARC-3140 and of its tetrabromo equivalent ARC-1502 on the CK2alpha/CK2beta interaction. A structural inspection revealed that ARC-3140, unlike CK2beta antagonists described so far, interferes with both sub-interfaces of the bipartite CK2alpha/CK2beta interaction. Thus, ARC-3140 is a lead for the further development of highly effective compounds perturbating the quaternary structure of the CK2alpha2beta2 holoenzyme. Unexpected CK2beta-antagonistic functionality of bisubstrate inhibitors targeting protein kinase CK2.,Pietsch M, Viht K, Schnitzler A, Ekambaram R, Steinkruger M, Enkvist E, Nienberg C, Nickelsen A, Lauwers M, Jose J, Uri A, Niefind K Bioorg Chem. 2020 Jan 23;96:103608. doi: 10.1016/j.bioorg.2020.103608. PMID:32058103 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Casein kinase 3D structures

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