title: Cyclic diguanylic acid behaves as a host molecule for planar intercalators.
abstract: 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').
authors.affiliation: Department of Physiology and Biophysics, University of Illinois, Urbana 61801.
authors.forename: Y C
authors.initials: YC
authors.lastname: Liaw
authors.forename: Y G
authors.initials: YG
authors.lastname: Gao
authors.forename: H
authors.initials: H
authors.lastname: Robinson
authors.forename: G M
authors.initials: GM
authors.lastname: Sheldrick
authors.forename: L A
authors.initials: LA
authors.lastname: Sliedregt
authors.forename: G A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: J H
authors.initials: JH
authors.lastname: van Boom
authors.forename: A H
authors.initials: AH
authors.lastname: Wang
mesh_terms: D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D006150:Guanine Nucleotides / Q000378:metabolism*; D006157:Guanosine Monophosphate / Q000031:analogs & derivatives / Q000378:metabolism*; D007364:Intercalating Agents; D015394:Molecular Structure; D013056:Spectrophotometry, Ultraviolet; D014961:X-Ray Diffraction
chemical_list: D006150:Guanine Nucleotides; D007364:Intercalating Agents; C024662:GpGp; C062025:bis(3',5')-cyclic diguanylic acid; D006157:Guanosine Monophosphate; D006152:Cyclic GMP