TY - JOUR
T1 - Cyclic diguanylic acid behaves as a host molecule for planar intercalators
AU - Liaw, Yen Chywan
AU - Gao, Yi Gui
AU - Robinson, Howard
AU - Sheldrick, George M.
AU - Sliedregt, L. A.J.M.
AU - van der Marel, Gijs A.
AU - van Boom, Jacques H.
AU - Wang, Andrew H.J.
N1 - Funding Information:
Acknowledgements: This work was supportedb y grantsf rom NSF and NIH (A.H.-J. W.). G.A.vdM. and JHvB. were supportedb y the NetherlandsO rganizationfo r the Advancemenot f Pure Research (ZWO).
PY - 1990/5/21
Y1 - 1990/5/21
N2 - 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').
AB - 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').
KW - DNA conformation
KW - DNA, cyclic
KW - Drug design
KW - Guest-host chemistry
KW - Metal-DNA interaction
KW - X-ray diffraction
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U2 - 10.1016/0014-5793(90)80253-F
DO - 10.1016/0014-5793(90)80253-F
M3 - Article
C2 - 2162785
AN - SCOPUS:0025362682
SN - 0014-5793
VL - 264
SP - 223
EP - 227
JO - FEBS Letters
JF - FEBS Letters
IS - 2
ER -