Liaw Y C, Gao Y G, Robinson H, Sheldrick G M, Sliedregt L A, van der Marel G A, van Boom J H, Wang A H
Department of Physiology and Biophysics, University of Illinois, Urbana 61801.
FEBS Lett. 1990 May 21;264(2):223-7. doi: 10.1016/0014-5793(90)80253-f.
Cyclic ribodiguanylic acid, c-(GpGp), is the endogenous effector regulator of cellulose synthase. Its three-dimensional structure from two different crystal forms (tetragonal and trigonal) has been determined by X-ray diffraction analysis at 1 A resolution. In both crystal forms, two independent c-(GpGp) molecules associate with each other to form a self-intercalated dimer. A hydrated cobalt ion is found to coordinate to two N7 atoms of adjacent guanines, forcing these two guanines to destack with a large dihedral angle (32 degrees), in the dimer of the tetragonal form. This metal coordination mechanism may be relevant to that of the anticancer drug cisplatin. Moreover, c-(GpGp) exhibits unusual spectral properties not seen in any other cyclic dinucleotide. It interacts with planar organic intercalator molecules in ways similar to double helical DNA. We propose a cage-like model consisting of a tetrameric c-(GpGp) aggregate in which a large cavity ('host') is generated to afford a binding site for certain planar intercalators ('guests').
环二鸟苷酸，c-(GpGp)，是纤维素合酶的内源性效应调节因子。通过1埃分辨率的X射线衍射分析确定了其两种不同晶体形式（四方晶系和三角晶系）的三维结构。在这两种晶体形式中，两个独立的c-(GpGp)分子相互缔合形成一个自插入二聚体。在四方晶系形式的二聚体中，发现一个水合钴离子与相邻鸟嘌呤的两个N7原子配位，迫使这两个鸟嘌呤以大的二面角（32度）解堆叠。这种金属配位机制可能与抗癌药物顺铂的机制相关。此外，c-(GpGp)表现出任何其他环二核苷酸都未见过的异常光谱性质。它与平面有机嵌入剂分子的相互作用方式类似于双螺旋DNA。我们提出了一个由四聚体c-(GpGp)聚集体组成的笼状模型，其中形成了一个大的空腔（“主体”），为某些平面嵌入剂（“客体”）提供一个结合位点。
