Battistutta Roberto, Mazzorana Marco, Sarno Stefania, Kazimierczuk Zygmunt, Zanotti Giuseppe, Pinna Lorenzo A
Department of Chemistry, University of Padua, via Marzolo 1, 35131 Padua, Italy.
Chem Biol. 2005 Nov;12(11):1211-9. doi: 10.1016/j.chembiol.2005.08.015.
CK2 is a very pleiotropic protein kinase whose high constitutive activity is suspected to cooperate to neoplasia. Here, the crystal structure of the complexes between CK2 and three selective tetrabromo-benzimidazole derivatives inhibiting CK2 with Ki values between 40 and 400 nM are presented. The ligands bind to the CK2 active site in a different way with respect to the parent compound TBB. They enter more deeply into the cavity, establishing halogen bonds with the backbone of Glu114 and Val116 in the hinge region. A detailed analysis of the interactions highlights a major role of the hydrophobic effect in establishing the rank of potency within this class of inhibitors and shows that polar interactions are responsible for the different orientation of the molecules in the active site.
CK2是一种具有多种功能的蛋白激酶，其高组成活性被怀疑与肿瘤形成有关。本文展示了CK2与三种选择性四溴苯并咪唑衍生物形成的复合物的晶体结构，这些衍生物对CK2具有抑制作用，其抑制常数（Ki）值在40至400 nM之间。与母体化合物TBB相比，这些配体以不同方式结合到CK2活性位点。它们更深地进入腔中，与铰链区的Glu114和Val116主链形成卤键。对相互作用的详细分析突出了疏水效应在确定这类抑制剂活性顺序中的主要作用，并表明极性相互作用导致分子在活性位点的不同取向。
