Cyclic diguanylic acid behaves as a host molecule for planar intercalators

FEBS Letters

Gao, Yi-Gui¹  Robinson, Howard¹  Sliedregt, L.A.J.M.³  Liaw, Yen-Chywan¹  Sheldrick, George M.²  van Boom, Jacques H.³  van der Marel, Gijs A.³  Wang, Andrew H.-J.¹ 

[1] Department of Physiology and Biophysics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA;Institut für Anorganische Chemie der Universität, Tammannstrasse 4, D-3400 Göttingen, FRG;Gorlaeus Laboratories, Leiden State University, 2300 RA Leiden, The Netherlands

关键词: Guest-host chemistry;    DNA;    cyclic;    X-ray diffraction;    Metal-DNA interaction;    Drug design;    DNA conformation;   

DOI  :  10.1016/0014-5793(90)80253-F

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 Å 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°), 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’).

【 授权许可】

Unknown