5OWH

High salt structure of human protein kinase CK2alpha in complex with 3-aminopropyl-4,5,6,7-tetrabromobenzimidazol

Summary for 5OWH

• Entry DOI: 10.2210/pdb5owh/pdb
• Descriptor: Casein kinase II subunit alpha, 3-[4,5,6,7-tetrakis(bromanyl)benzimidazol-1-yl]propan-1-amine, CHLORIDE ION, ... (4 entities in total)
• Functional Keywords: protein kinase ck2 casein kinase 2 atp-competitive inhibitor 3-aminopropyl-4, 5, 6, 7-tetrabromobenzimidazol, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 40593.01

Authors

Niefind, K.,Bretner, M.,Chojnacki, C. (deposition date: 2017-09-01, release date: 2018-07-25, Last modification date: 2024-01-17)

Primary citation

Chojnacki, K.,Winska, P.,Wielechowska, M.,Lukowska-Chojnacka, E.,Tolzer, C.,Niefind, K.,Bretner, M.
Biological properties and structural study of new aminoalkyl derivatives of benzimidazole and benzotriazole, dual inhibitors of CK2 and PIM1 kinases.
Bioorg. Chem., 80:266-275, 2018

PubMed Abstract: The new aminoalkyl-substituted derivatives of known CK2 inhibitors 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt) were synthesized, and their influence on the activity of recombinant human CK2 α, CK2 holoenzyme and PIM1 kinases was evaluated. All derivatives inhibited the activity of studied kinases and the most efficient were aminopropyl-derivatives 8b and 14b. These compounds also exerted inhibition of cancer cell lines - CCRF-CEM (acute lymphoblastoid leukemia), MCF-7 (human breast cancer), and PC-3 (prostate cancer) proliferation and their EC is comparable with the value for clinically studied CK2 inhibitor CX-4945. Preliminary structure activity relationship analysis indicated that the spacer length affected antitumor potency, and two to three methylene units were more favorable. The complex of CK2 α/8b was crystallized, both under high-salt conditions and under low-salt conditions giving crystals which diffracted X-rays to about 2.4 Å resolution, what enabled the determination of the corresponding 3D-structures.

PubMed: 29966873
DOI: 10.1016/j.bioorg.2018.06.022

Experimental method

X-RAY DIFFRACTION (2.3 Å)