title: NMR and molecular modeling evidence for a G.A mismatch base pair in a purine-rich DNA duplex.
abstract: 1H NMR experiments indicate that the oligomer 5'-d(ATGAGCGAATA) forms an unusual 10-base-pair duplex with 4 G.A base pairs (underlined) and a 3' unpaired adenosine. NMR results indicate that guanosine imino protons of the G.A mismatches are not hydrogen bonded but are stacked in the helix. A G----I substitution in either G.A base pair causes a dramatic decrease in duplex stability and indicates that hydrogen bonding of the guanosine amino group is critical. Nuclear Overhauser effect spectroscopy (NOESY) and two-dimensional correlated spectroscopy (COSY) results indicate that the overall duplex conformation is in the B-family. Cross-strand NOEs in two-dimensional NOESY spectra between a mismatched AH2 and an AH1' of the other mismatched base pair and between a mismatched GH8 and GNH1 of the other mismatch establish a purine-purine stacking pattern, adenosine over adenosine and guanosine over guanosine, which strongly stabilizes the duplex. A computer graphics molecular model of the unusual duplex was constructed with G.A base pairs containing A-NH2 to GN3 and G-NH2 to AN7 hydrogen bonds and B-form base pairs on both sides of the G.A pairs [5'-d(ATGAGC)]. The energy-minimized duplex satisfies all experimental constraints from NOESY and COSY results. A hydrogen bond from G-NH2 of the mismatch to a phosphate oxygen is predicted.
authors.affiliation: Department of Chemistry, Georgia State University, Atlanta 30303-3083.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: G
authors.initials: G
authors.lastname: Zon
authors.forename: W D
authors.initials: WD
authors.lastname: Wilson
mesh_terms: D000225:Adenine; D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D006147:Guanine; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*
chemical_list: D009838:Oligodeoxyribonucleotides; D006147:Guanine; D004247:DNA; D000225:Adenine