4fbx

Complex structure of human protein kinase CK2 catalytic subunit crystallized in the presence of a bisubstrate inhibitorComplex structure of human protein kinase CK2 catalytic subunit crystallized in the presence of a bisubstrate inhibitor

Structural highlights 4fbx is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NonStd Res: Related: 3bqc, 1jwh, 3nsz, 3ofm, 1lp4 Gene: CSNK2A1, CK2A1 (Homo sapiens) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Up-regulation of an acidophilic protein kinase, CK2, has been established in several types of cancer. This cognition has made CK2 an important target for drug development for cancer chemotherapy. The characterization of potential drug candidates, determination of the structure and clarification of the functions of CK2 could be facilitated by the application of small-molecule fluorescent probes that bind to the active site of the enzyme with high affinity and selectivity. We have used a bisubstrate approach for the development of a highly potent inhibitor of CK2. 4,5,6,7-Tetrabromo-1H-benzimidazole was conjugated with peptides containing multiple aspartate residues via different linkers. The design of the inhibitors was by crystallographic analysis of the complex of an inhibitor with the catalytic subunit of the enzyme (CK2alpha). The inhibitory potency of the synthesized compounds was established in a kinetic assay that used thin layer chromatography for the measurement of the rate of phosphorylation of fluorescently labelled peptide 5-TAMRA-RADDSDDDDD. The most potent inhibitor, ARC-1502 (K(i) = 0.5 nM), revealed high selectivity for CK2alpha in a panel of 140 protein kinases. Labelling of ARC-1502 with PromoFluor-647 gave the fluorescent probe ARC-1504 that possessed subnanomolar affinity towards both CK2alpha and the holoenzyme. The probe was used in a fluorescence anisotropy-based binding assay to measure the concentration of CK2alpha and characterize non-labelled ligands binding to the active site of CK2alpha. A subnanomolar fluorescent probe for protein kinase CK2 interaction studies.,Enkvist E, Viht K, Bischoff N, Vahter J, Saaver S, Raidaru G, Issinger OG, Niefind K, Uri A Org Biomol Chem. 2012 Oct 2. PMID:23032938 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Casein kinase

spinqualitylabelsall models 4fbx, resolution 2.33Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image