3E3B

Crystal structure of catalytic subunit of human protein kinase CK2alpha prime with a potent indazole-derivative inhibitor

3E3B の概要

• エントリーDOI: 10.2210/pdb3e3b/pdb
• 分子名称: Casein kinase II subunit alpha', [1-(6-{6-[(1-methylethyl)amino]-1H-indazol-1-yl}pyrazin-2-yl)-1H-pyrrol-3-yl]acetic acid (3 entities in total)
• 機能のキーワード: casein kinase 2, ck2alpha prime, ck2alpha inhibitor, selective kinase inhibitor, atp-binding, kinase, nucleotide-binding, polymorphism, serine/threonine-protein kinase, transferase, wnt signaling pathway
• 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: 40536.40

構造登録者

Kinoshita, T.,Nakaniwa, T.,Tada, T. (登録日: 2008-08-07, 公開日: 2009-03-03, 最終更新日: 2023-11-01)

主引用文献

Nakaniwa, T.,Kinoshita, T.,Sekiguchi, Y.,Tada, T.,Nakanishi, I.,Kitaura, K.,Suzuki, Y.,Ohno, H.,Hirasawa, A.,Tsujimoto, G.
Structure of human protein kinase CK2alpha2 with a potent indazole-derivative inhibitor
Acta Crystallogr.,Sect.F, 65:75-79, 2009

PubMed Abstract: Casein kinase 2 (CK2) is a serine/threonine kinase that functions as a heterotetramer composed of two catalytic subunits (CK2alpha1 or CK2alpha2) and two regulatory subunits (CK2beta). The two isozymes CK2alpha1 and CK2alpha2 play distinguishable roles in healthy subjects and in patients with diseases such as cancer, respectively. In order to develop novel CK2alpha1-selective inhibitors, the crystal structure of human CK2alpha2 (hCK2alpha2) complexed with a potent CK2alpha inhibitor which binds to the active site of hCK2alpha2 was determined and compared with that of human CK2alpha1. While the two isozymes exhibited a high similarity with regard to the active site, the largest structural difference between the isoforms occurred in the beta4-beta5 loop responsible for the CK2alpha-CK2beta interface. The top of the N-terminal segment interacted with the beta4-beta5 loop via a hydrogen bond in hCK2alpha2 but not in hCK2alpha1. Thus, the CK2alpha-CK2beta interface is a likely target candidate for the production of selective CK2alpha1 inhibitors.

PubMed: 19193990
DOI: 10.1107/S1744309108043194

実験手法

X-RAY DIFFRACTION (3.2 Å)