| Autor: |
Pfaff DA; Department of Chemistry and Biochemistry, University of San Diego, San Diego, California 92110, USA., Clarke KM, Parr TA, Cole JM, Geierstanger BH, Tahmassebi DC, Dwyer TJ |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Chemical Society [J Am Chem Soc] 2008 Apr 09; Vol. 130 (14), pp. 4869-78. Date of Electronic Publication: 2008 Mar 15. |
| DOI: |
10.1021/ja7103608 |
| Abstrakt: |
The incorporation of synthetic nucleoside analogues into DNA duplexes provides a unique opportunity to probe both structure and function of nucleic acids. We used 1H and 19F NMR and molecular dynamics calculations to determine the solution structures of two similar DNA decamer duplexes, one containing a central G-T mismatched or "wobble" base pair, and one in which the thymine in this base pair is replaced by difluorotoluene (a thymine isostere) creating a G-F pair. Here, we show that the non-hydrogen-bonding G-F pair stacks relatively well into the helix and that the distortions caused by each non-Watson-Crick G-T or G-F base pair are quite localized to a three base pair site around the mismatch. A detailed structural analysis reveals that the absence of hydrogen bonding introduces more dynamic motion into the G-F pair relative to G-T and permits the G-F pair to exhibit stacking and conformational features characteristic of both a Watson-Crick base pair (on the guanine containing strand) and a wobble base pair (on the strand containing the difluorotoluene). We used these results to posit a rationale for recognition and repair of mismatch sites in DNA. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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