title: The solution structure of [d(CGC)r(aaa)d(TTTGCG)](2): hybrid junctions flanked by DNA duplexes.
abstract: The solution structure and hydration of the chimeric duplex [d(CGC)r(aaa)d(TTTGCG)](2), in which the central hybrid segment is flanked by DNA duplexes at both ends, was determined using two-dimensional NMR, simulated annealing and restrained molecular dynamics. The solution structure of this chimeric duplex differs from the previously determined X-ray structure of the analogous B-DNA duplex [d(CGCAAATTTGCG)](2)as well as NMR structure of the analogous A-RNA duplex [r(cgcaaauuugcg)](2). Long-lived water molecules with correlation time tau(c)longer than 0.3 ns were found close to the RNA adenine H2 and H1' protons in the hybrid segment. A possible long-lived water molecule was also detected close to the methyl group of 7T in the RNA-DNA junction but not with the other two thymines (8T and 9T). This result correlates with the structural studies that only DNA residue 7T in the RNA-DNA junction adopts an O4'-endo sugar conformation, while the other DNA residues including 3C in the DNA-RNA junction, adopt C1'-exo or C2'-endo conformations. The exchange rates for RNA C2'-OH were found to be approximately 5-20 s(-1). This slow exchange rate may be due to the narrow minor groove width of [d(CGC)r(aaa)d(TTTGCG)](2), which may trap the water molecules and restrict the dynamic motion of hydroxyl protons. The minor groove width of [d(CGC)r(aaa)d(TTTGCG)](2)is wider than its B-DNA analog but narrower than that of the A-RNA analog. It was further confirmed by its titration with the minor groove binding drug distamycin. A possible 2:1 binding mode was found by the titration experiments, suggesting that this chimeric duplex contains a wider minor groove than its B-DNA analog but still narrow enough to hold two distamycin molecules. These distinct structural features and hydration patterns of this chimeric duplex provide a molecular basis for further understanding the structure and recognition of DNA. RNA hybrid and chimeric duplexes.
authors.affiliation: Division of Structural Biology and Biomedical Science, Department of Life Science, National Tsing Hua University, Hsinchu 300, Taiwan, Republic of China.
authors.forename: S T
authors.initials: ST
authors.lastname: Hsu
authors.forename: M T
authors.initials: MT
authors.lastname: Chou
authors.forename: J W
authors.initials: JW
authors.lastname: Cheng
mesh_terms: D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004214:Distamycins / Q000378:metabolism / Q000494:pharmacology; D006207:Half-Life; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009692:Nucleic Acid Heteroduplexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011522:Protons; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012996:Solutions; D017186:Titrimetry; D014867:Water / Q000378:metabolism
chemical_list: D004214:Distamycins; D009692:Nucleic Acid Heteroduplexes; D011522:Protons; D012996:Solutions; D014867:Water; D012313:RNA; C030000:stallimycin; D004247:DNA