Structure of human protein kinase CK2α2 with a potent indazole‐derivative inhibitor
Casein kinase 2 (CK2) is a serine/threonine kinase that functions as a heterotetramer composed of two catalytic subunits (CK2α1 or CK2α2) and two regulatory subunits (CK2β). The two isozymes CK2α1 and CK2α2 play distinguishable roles in healthy subjects and in patients with diseases such as cancer, respectively. In order to develop novel CK2α1‐selective inhibitors, the crystal structure of human CK2α2 (hCK2α2) complexed with a potent CK2α inhibitor which binds to the active site of hCK2α2 was determined and compared with that of human CK2α1. While the two isozymes exhibited a high similarity with regard to the active site, the largest structural difference between the isoforms occurred in the β4–β5 loop responsible for the CK2α–CK2β interface. The top of the N‐terminal segment interacted with the β4–β5 loop via a hydrogen bond in hCK2α2 but not in hCK2α1. Thus, the CK2α–CK2β interface is a likely target candidate for the production of selective CK2α1 inhibitors.
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