Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1995 May 25;23(10):1810–1815. doi: 10.1093/nar/23.10.1810

Solution structure of a nucleic acid photoproduct of deoxyfluorouridylyl-(3'-5')-thymidine monophosphate (d-FpT) determined by NMR and restrained molecular dynamics: structural comparison of two sequence isomer photoadducts (d-U5p5T and d-T5p5U).

J K Kim 1, S D Soni 1, A V Arakali 1, J C Wallace 1, J L Alderfer 1
PMCID: PMC306940  PMID: 7784187

Abstract

Acetone-sensitized irradiation using UV-B (sun lamp, lambda max = 313 nm) of deoxyfluorouridylyl-(3'-5')-thymidine monophosphate (d-FpT, F = fluorouracil), produces two major photoproducts, the cis-syn cyclobutane-type photodimer and a defluorinated (5-5) photoadduct, d-U5p5T. Product distribution is dependent on the pH of the irradiation solution, as was the case of irradiated d-TpF. At high pH (8-10) the (5-5) photoadduct is the major photoproduct. Irradiation of d-FpT shows a much faster photodegradation rate than the sequence isomer d-TpF. Multinuclear NMR experiments establish the formation of (5-5) covalent bonding between the C5 (d-U5p-, where the fluorine had been) and the C5 (-p5T) and the C6 (-p5T) acquires an OH group. NOE interproton distances and dihedral angles derived from J coupling analysis are constrained to refine model structures of d-U5p5T in restrained molecular dynamics calculations. The resultant structures obtained show 5S-6S as the most chiralities of the C5 and C6 atoms of the thymine, which is the opposite chirality to the corresponding atoms in the sequence isomer d-T5p5U. The orientation of the C5 substituents (-p5T fragment), the CH3 and the uracil are pseudo-axial and pseudo-equatorial respectively. Glycosidic angles are in the anti regions for both the d-U5p- and -p5T residues. Averaged backbone conformations of the two photoadducts, d-U5p5T and d-T5p5U, are similar, although the overall structure of d-U5p5T appears much more flexible than that of d-T5p5U. In particular, the sugar conformations of the 5'-end residues show a remarkable difference in flexibility.

Full text

PDF
1810

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alderfer J. L., Soni S. D., Arakali A. V., Wallace J. C. UV irradiation of nucleic acids: characterization of photoproducts of thymidylyl-(3'-->5')-2'-deoxy-5-fluorouridine. Photochem Photobiol. 1993 May;57(5):770–776. doi: 10.1111/j.1751-1097.1993.tb09209.x. [DOI] [PubMed] [Google Scholar]
  2. Cadet J., Ducolomb R., Hruska F. E. Proton magnetic resonance studies of 5,6-saturated thymidine derivatives produced by ionizing radiation. Conformational analysis of 6-hydroxylated diastereoisomers. Biochim Biophys Acta. 1979 Jun 20;563(1):206–215. doi: 10.1016/0005-2787(79)90021-2. [DOI] [PubMed] [Google Scholar]
  3. DELLWEG H., WACKER A. STRAHLENCHEMISCHE VERAENDERUNG DER 5-HALOGEN-URACILE IN DER DNS DURCH UV-STRAHLEN. Z Naturforsch B. 1964 Apr;19:305–311. [PubMed] [Google Scholar]
  4. Goz B. The effects of incorporation of 5-halogenated deoxyuridines into the DNA of eukaryotic cells. Pharmacol Rev. 1977 Dec;29(4):249–272. [PubMed] [Google Scholar]
  5. Ishihara H., Wang S. Y. Photochemistry of 5-bromouracil in aqueous solution. Biochemistry. 1966 Jul;5(7):2307–2313. doi: 10.1021/bi00871a020. [DOI] [PubMed] [Google Scholar]
  6. Kim J. K., Soni S. D., Wallace J. C., Alderfer J. L. Solution structure of nucleic acid photoadduct, deoxy-m5HO6-uridylyl(5-5)(3'-5')deoxyuridine by NMR and restrained molecular dynamics. Nucleic Acids Res. 1993 Jun 11;21(11):2755–2759. doi: 10.1093/nar/21.11.2755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Koning T. M., Davies R. J., Kaptein R. The solution structure of the intramolecular photoproduct of d(TpA) derived with the use of NMR and a combination of distance geometry and molecular dynamics. Nucleic Acids Res. 1990 Jan 25;18(2):277–284. doi: 10.1093/nar/18.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Marion D., Wüthrich K. Application of phase sensitive two-dimensional correlated spectroscopy (COSY) for measurements of 1H-1H spin-spin coupling constants in proteins. Biochem Biophys Res Commun. 1983 Jun 29;113(3):967–974. doi: 10.1016/0006-291x(83)91093-8. [DOI] [PubMed] [Google Scholar]
  9. Taylor J. S., Garrett D. S., Wang M. J. Models for the solution state structure of the (6-4) photoproduct of thymidylyl-(3'----5')-thymidine derived via a distance- and angle-constrained conformation search procedure. Biopolymers. 1988 Oct;27(10):1571–1593. doi: 10.1002/bip.360271004. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES