6YPJ

Crystal Structure of CK2alpha with Compound 1 bound

6YPJ の概要

• エントリーDOI: 10.2210/pdb6ypj/pdb
• 分子名称: Casein kinase II subunit alpha, ACETATE ION, 4-[(4-phenyl-1,3-thiazol-2-yl)amino]benzoic acid, ... (4 entities in total)
• 機能のキーワード: selective atp competitive inhibitors, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 39386.78

構造登録者

Brear, P.,Hyvonen, M. (登録日: 2020-04-16, 公開日: 2020-07-15, 最終更新日: 2024-01-24)

主引用文献

Brear, P.,Ball, D.,Stott, K.,D'Arcy, S.,Hyvonen, M.
Proposed Allosteric Inhibitors Bind to the ATP Site of CK2 alpha.
J.Med.Chem., 63:12786-12798, 2020

PubMed Abstract: CK2α is a ubiquitous, well-studied kinase that is a target for small-molecule inhibition, for treatment of cancers. While many different classes of adenosine 5'-triphosphate (ATP)-competitive inhibitors have been described for CK2α, they tend to suffer from significant off-target activity and new approaches are needed. A series of inhibitors of CK2α has recently been described as allosteric, acting at a previously unidentified binding site. Given the similarity of these inhibitors to known ATP-competitive inhibitors, we have investigated them further. In our thorough structural and biophysical analyses, we have found no evidence that these inhibitors bind to the proposed allosteric site. Rather, we report crystal structures, competitive isothermal titration calorimetry (ITC) and NMR, hydrogen-deuterium exchange (HDX) mass spectrometry, and chemoinformatic analyses that all point to these compounds binding in the ATP pocket. Comparisons of our results and experimental approach with the data presented in the original report suggest that the primary reason for the disparity is nonspecific inhibition by aggregation.

PubMed: 33119282
DOI: 10.1021/acs.jmedchem.0c01173

実験手法

X-RAY DIFFRACTION (1.64 Å)