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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1994-2-22
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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.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cisplatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cobalt,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/Platinum,
http://linkedlifedata.com/resource/pubmed/chemical/bis(3',5')-cyclic diguanylic acid,
http://linkedlifedata.com/resource/pubmed/chemical/cisplatin-DNA adduct
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0739-1102
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
253-76
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:8286055-Base Sequence,
pubmed-meshheading:8286055-Binding Sites,
pubmed-meshheading:8286055-Cisplatin,
pubmed-meshheading:8286055-Cobalt,
pubmed-meshheading:8286055-Computer Simulation,
pubmed-meshheading:8286055-Crystallography, X-Ray,
pubmed-meshheading:8286055-Cyclic GMP,
pubmed-meshheading:8286055-DNA,
pubmed-meshheading:8286055-DNA Adducts,
pubmed-meshheading:8286055-Hydrogen Bonding,
pubmed-meshheading:8286055-Models, Molecular,
pubmed-meshheading:8286055-Molecular Sequence Data,
pubmed-meshheading:8286055-Nucleic Acid Conformation,
pubmed-meshheading:8286055-Platinum,
pubmed-meshheading:8286055-Spectrophotometry, Ultraviolet
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pubmed:year |
1993
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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.
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pubmed:affiliation |
Division of Biophysics, University of Illinois at Urbana-Champaign 61801.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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