title: Solution conformation of an oligonucleotide containing a G.G mismatch determined by nuclear magnetic resonance and molecular mechanics.
abstract: We have determined by two-dimensional nuclear magnetic resonance studies and molecular mechanics calculations the three dimensional solution structure of the non-selfcomplementary oligonucleotide, d(GAGGAGGCACG). d(CGTGCGTCCTC) in which the central base pair is G.G. This is the first structural determination of a G.G mismatch in a oligonucleotide. Two dimensional nuclear magnetic resonance spectra show that the bases of the mismatched pair are stacked into the helix and that the helix adopts a classical B-DNA form. Spectra of the exchangeable protons show that the two guanosines are base paired via their imino protons. For the non-exchangeable protons and for some of the exchangeable protons nuclear Overhauser enhancement build up curves at short mixing times have been measured. These give 84 proton-proton distances which are sensitive to the helix conformation. One of the guanosines adopts a normal anti conformation while the other is syn or close to syn. All non-terminal sugars are C2' endo. These data sets were incorporated into the refinement of the oligonucleotide structure by molecular mechanics calculations. The G.G mismatch shows a symmetrical base pairing structure. Although the mismatch is very bulky many of its features are close to that of normal B-DNA. The mismatch induces a small lateral shift in the helix axis and the sum of the helical twist above and below the mismatch is close to that of B-DNA.
authors.affiliation: Laboratoire de Physico-chimie Macromoléculaire, Institut Gustave Roussy, Villejuif, France.
authors.forename: J A
authors.initials: JA
authors.lastname: Cognet
authors.forename: J
authors.initials: J
authors.lastname: Gabarro-Arpa
authors.forename: M
authors.initials: M
authors.lastname: Le Bret
authors.forename: G A
authors.initials: GA
authors.lastname: van der Marel
authors.forename: J H
authors.initials: JH
authors.lastname: van Boom
authors.forename: G V
authors.initials: GV
authors.lastname: Fazakerley
mesh_terms: D010582:Bacteriophage lambda / Q000235:genetics; D001483:Base Sequence; D004260:DNA Repair / Q000235:genetics; D006151:Guanosine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry* / Q000235:genetics; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000235:genetics
chemical_list: D009692:Nucleic Acid Heteroduplexes; D009838:Oligodeoxyribonucleotides; D006151:Guanosine