title: Solution structure of a pyrimidine.purine.pyrimidine DNA triplex containing T.AT, C+.GC and G.TA triples.
abstract: BACKGROUND
  Under certain conditions, homopyrimidine oligonucleotides can bind to complementary homopurine sequences in homopurine-homopyrimidine segments of duplex DNA to form triple helical structures. Besides having biological implications in vivo, this property has been exploited in molecular biology applications. This approach is limited by a lack of knowledge about the recognition by the third strand of pyrimidine residues in Watson-Crick base pairs.
  
  
  RESULTS
  We have therefore determined the solution structure of a pyrimidine.purine.pyrimidine (Y.RY) DNA triple helix containing a guanine residue in the third strand which was postulated to specifically recognize a thymine residue in a Watson-Crick TA base pair. The structure was solved by combining NMR-derived restraints with molecular dynamics simulations conducted in the presence of explicit solvent and counter ions. The guanine of the G-TA triple is tilted out of the plane of its target TA base pair towards the 3'-direction, to avoid a steric clash with the thymine methyl group. This allows the guanine amino protons to participate in hydrogen bonds with separate carbonyls, forming one strong bond within the G-TA triple and a weak bond to an adjacent T.AT triple. Dramatic variations in helical twist around the guanine residue lead to a novel stacking interaction. At the global level, the Y.RY DNA triplex shares several structural features with the recently solved solution structure of the R.RY DNA triplex.
  
  
  CONCLUSIONS
  The formation of a G.TA triple within an otherwise pyrimidine.purine.pyrimidine DNA triplex causes conformational realignments in and around the G.TA triple. These highlight new aspects of molecular recognition that could be useful in triplex-based approaches to inhibition of gene expression and site-specific cleavage of genomic DNA.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
authors.forename: I
authors.initials: I
authors.lastname: Radhakrishnan
authors.forename: D J
authors.initials: DJ
authors.lastname: Patel
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D011687:Purines; D011743:Pyrimidines; D012996:Solutions; D013314:Stress, Mechanical
chemical_list: D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D011687:Purines; D011743:Pyrimidines; D012996:Solutions; D004247:DNA