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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-2-22
pubmed:abstractText
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. Both structures were solved by direct methods and refined by block-matrix least squares refinement to R-factors of 0.112 (tetragonal) and 0.119 (trigonal). In both crystal forms, two independent c-(GpGp) molecules associate with each other to form a self-intercalated dimer. All four c-(GpGp) molecules have very similar backbone conformation. The riboses are in the C3'-endo pucker with pseudorotation angles ranging from -7.2 degrees to 16.5 degrees and the bases have anti glycosyl chi angles (-175.5 degrees to 179.7 degrees). In the tetragonal form, 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 (33 degrees). This metal coordination mechanism has been noted previously in other Pt- or Co-GMP complexes and may be relevant to the binding of the anticancer drug cisplatin to a GpG sequence in DNA. A model of the adduct between cisplatin and a d(CAATGGATTG) duplex has been constructed in which the induced bending of the DNA helix at the Pt crosslinking site is 33 degrees, consistent with earlier electrophoretic analyses. Moreover, c-(GpGp) exhibits unusual spectral properties not seen in other cyclic dinucleotides. 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 molecule) is generated to afford a binding site for certain planar intercalators (guests molecules). The aggregate likely uses a hydrogen bonding scheme the same as that found in the G-quartet molecules, e.g., telomere DNA. The conformation of c-(GpGp) also suggests that certain nearest-neighbor intercalators may be synthesized on the basis of its unique molecular framework. Modeling studies have been carried out to test this hypothesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0739-1102
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
253-76
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Molecular structure of cyclic diguanylic acid at 1 A resolution of two crystal forms: self-association, interactions with metal ion/planar dyes and modeling studies.
pubmed:affiliation
Division of Biophysics, University of Illinois at Urbana-Champaign 61801.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.