1J91

Crystal structure of Z. mays CK2 kinase alpha subunit in complex with the ATP-competitive inhibitor 4,5,6,7-tetrabromobenzotriazole

Summary for 1J91

• Entry DOI: 10.2210/pdb1j91/pdb
• Descriptor: CASEIN KINASE II, ALPHA CHAIN, 4,5,6,7-TETRABROMOBENZOTRIAZOLE (3 entities in total)
• Functional Keywords: ck2, casein kinase 2, inhibitors, tetrabromo-benzotriazole, transferase
• Biological source: Zea mays
• Total number of polymer chains: 2
• Total formula weight: 79451.74

Authors

Battistutta, R.,De Moliner, E.,Sarno, S.,Zanotti, G.,Pinna, L.A. (deposition date: 2001-05-23, release date: 2002-05-29, Last modification date: 2024-02-07)

Primary citation

Battistutta, R.,De Moliner, E.,Sarno, S.,Zanotti, G.,Pinna, L.A.
Structural features underlying selective inhibition of protein kinase CK2 by ATP site-directed tetrabromo-2-benzotriazole.
Protein Sci., 10:2200-2206, 2001

PubMed Abstract: Two novel crystal structures of Zea mays protein kinase CK2alpha catalytic subunit, one in complex with the specific inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB) and another in the apo-form, were solved at 2.2 A resolution. These structures were compared with those of the enzyme in presence of ATP and GTP (the natural cosubstrates) and the inhibitor emodin. Interaction of TBB with the active site of CK2alpha is mainly due to van der Waals contacts, with the ligand fitting almost perfectly the cavity. One nitrogen of the five-membered ring interacts with two charged residues, Glu 81 and Lys 68, in the depth of the cavity, through two water molecules. These are buried in the active site and are also generally found in the structures of CK2alpha enzyme analyzed so far, with the exception of the complex with emodin. In the N-terminal lobe, the position of helix alphaC is particularly well preserved in all the structures examined; the Gly-rich loop is displaced from the intermediate position it has in the apo-form and in the presence of the natural cosubstrates (ATP/GTP) to either an upper (with TBB) or a lower position (with emodin). The selectivity of TBB for CK2 appears to be mainly dictated by the reduced size of the active site which in most other protein kinases is too large for making stable interactions with this inhibitor.

PubMed: 11604527
DOI: 10.1110/ps.19601

Experimental method

X-RAY DIFFRACTION (2.22 Å)