3E3B

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

Summary for 3E3B

• Entry DOI: 10.2210/pdb3e3b/pdb
• Descriptor: 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)
• Functional Keywords: casein kinase 2, ck2alpha prime, ck2alpha inhibitor, selective kinase inhibitor, atp-binding, kinase, nucleotide-binding, polymorphism, serine/threonine-protein kinase, transferase, wnt signaling pathway
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 40536.40

Authors

Kinoshita, T.,Nakaniwa, T.,Tada, T. (deposition date: 2008-08-07, release date: 2009-03-03, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.2 Å)