Cyclic diguanylic acid behaves as a host molecule for planar intercalators

Yen Chywan Liaw, Yi Gui Gao, Howard Robinson, George M. Sheldrick, L. A.J.M. Sliedregt, Gijs A. van der Marel, Jacques H. van Boom, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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 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').

Original languageEnglish
Pages (from-to)223-227
Number of pages5
JournalFEBS Letters
Volume264
Issue number2
DOIs
Publication statusPublished - May 21 1990
Externally publishedYes

Keywords

  • DNA conformation
  • DNA, cyclic
  • Drug design
  • Guest-host chemistry
  • Metal-DNA interaction
  • X-ray diffraction

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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