ArticleActa pharmacologica Sinica2017
A novel allosteric site in casein kinase 2α discovered using combining bioinformatics and biochemistry methods.
Article in Acta pharmacologica Sinica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 23 citations in OpenAlex.
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis.Journal of advanced research · 2025Article
- Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α.Cell chemical biology · 2024Article
- Serine/Threonine Protein Kinases as Attractive Targets for Anti-Cancer Drugs-An Innovative Approach to Ligand Tuning Using Combined Quantum Chemical Calculations, Molecular Docking, Molecular Dynamic Simulations, and Network-like Similarity Graphs.Molecules (Basel, Switzerland) · 2024Article
- Recent Advances in the Discovery of CK2 Inhibitors.ACS omega · 2024Review
- Chemoproteomics reveals immunogenic and tumor-associated cell surface substrates of ectokinase CK2α.bioRxiv : the preprint server for biology · 2024Article
- Identification of the Allosteric Binding Site for Thiazolopyrimidine on the C-Type Lectin Langerin.ACS chemical biology · 2022Article
- Long non-coding RNA B3GALT5-AS1 contributes to the progression of gastric cancer via interacting with CSNK2A1.Experimental and therapeutic medicine · 2021Article
- Big data and artificial intelligence discover novel drugs targeting proteins without 3D structure and overcome the undruggable targets.Stroke and vascular neurology · 2020Review
- Recent Advances in the Discovery of CK2 Allosteric Inhibitors: From Traditional Screening to Structure-Based Design.Molecules (Basel, Switzerland) · 2020Review
- Identification and Biological Evaluation of CK2 Allosteric Fragments through Structure-Based Virtual Screening.Molecules (Basel, Switzerland) · 2020Article
- Protein Kinase CK2 in Cancer Energetics.Frontiers in oncology · 2020Review
- AlloFinder: a strategy for allosteric modulator discovery and allosterome analyses.Nucleic acids research · 2018Article
- Article
- Insights into the Impact of Linker Flexibility and Fragment Ionization on the Design of CK2 Allosteric Inhibitors: Comparative Molecular Dynamics Simulation Studies.International journal of molecular sciences · 2018Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Casein kinase 2 (CK2) is a highly pleiotropic serine-threonine kinase, which catalyzed phosphorylation of more than 300 proteins that are implicated in regulation of many cellular functions, such as signal transduction, transcriptional control, apoptosis and the cell cycle. On the other hand, CK2 is abnormally elevated in a variety of tumors, and is considered as a promising therapeutic target. The currently available ATP-competitive CK2 inhibitors, however, lack selectivity, which has impeded their development in cancer therapy. Because allosteric inhibitors can avoid the shortcomings of conventional kinase inhibitors, this study was aimed to discover a new allosteric site in CK2α and to investigate the effects of mutations in this site on the activity of CK2α. Using Allosite based on protein dynamics and structural alignment, we predicted a new allosteric site that was partly located in the αC helix of CK2α. Five residues exposed on the surface of this site were mutated to validate the prediction. Kinetic analyses were performed using a luminescent ADP detection assay by varying the concentrations of a peptide substrate, and the results showed that the mutations I78C and I78W decreased CK2α activity, whereas V31R, K75E, I82C and P109C increased CK2α activity. Potential allosteric pathways were identified using the Monte Carlo path generation approach, and the results of these predicted allosteric pathways were consistent with the mutation analysis. Multiple sequence alignments of CK2α with the other kinases in the family were conducted using the ClustalX method, which revealed the diversity of the residues in the site. In conclusion, we identified a new allosteric site in CK2α that can be altered to modulate the activity of the kinase. Because of the high diversity of the residues in the site, the site can be targeted using rational drug design of specific CK2α inhibitors for biological relevance.
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