Cyclic diguanylic acid behaves as a host molecule for planar intercalators.
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').
Liaw
Y C
YC
Department of Physiology and Biophysics, University of Illinois, Urbana 61801.
Gao
Y G
YG
Robinson
H
H
Sheldrick
G M
GM
Sliedregt
L A
LA
van der Marel
G A
GA
van Boom
J H
JH
Wang
A H
AH
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
D006150:Guanine Nucleotides; D007364:Intercalating Agents; C024662:GpGp; C062025:bis(3',5')-cyclic diguanylic acid; D006157:Guanosine Monophosphate; D006152:Cyclic GMP