Structure and dynamics of nucleic acids photoproducts
Sensitized UV-B irradiation of the dinucleoside monophosphate, d-TpF and d-FpT (F = fluorouracil), produces a defluorinated (5-5) photoadduct, d-T5p5U and d-U5p5T. 2D-NOE experiments and restrained molecular dynamics calculation produced three dimensional structures of the two (5-5) photoadducts, where a 5R-6R and a 5S-6S configuration were obtained as the most probable chiralities of the TC5 and TC6 atoms in d-T5p5U and d-U5p5T. The conformation of cyclobutane-ring (CB-ring) of cis-syn type photodimer revealed potential importance in the photolyase-substrate interactions and conformational impacts on normal nucleic acid regions. In the two puckering modes (CB[sup +] and CB[sup [minus]]) cyclobutane rings are twisted in right-handed fashion as are the base in B-DNA (CB[sup +]) or are left-handed twisted (CB[sup [minus]]). c-s d-T[p]T shows a flexibilities of the CB-ring (CB[sup +] [leftrightarrow] CB[sup [minus]]) and the glycosidic bonds (syn [leftrightarrow] anti), while in c-s-r-U[p]U only the CB[sup [minus]] mode was observed with syn and anti at the 5'-side and 3'-side glycosidic bond. In the ROESY experiment of d(T)[sub 4] containing photodimer, the CB-ring and the 5'-side glycosidic bond at the dimers site showed reduced flexibility. In studies of c-s d-T[p]U, c-s d-U[p]T and c-s d-U[p]U, the methyl group in DNA type photodimer is crucial for inducing the CB-ring flexibility, and 2'-OH group affect the flexibility of 5'-side glycosidic bond in the dimer. Molecular modeling, mechanics and dynamics were used to investigate the conformational behaviors of the photodimerized DNA and RNA structure. Photodimerized RNA structure produced the large structural distortions over the wide regions including the dimer site with the least RMS values of intradimer backbone torsions, while in the dimerized DNA, structural distortions were observed at the first and third residues to the 5'-side and the 3'-side of the dimer site, respectively, but not at the dimer site.
- Research Organization:
- State Univ. of New York, Buffalo, NY (United States)
- OSTI ID:
- 7042701
- Resource Relation:
- Other Information: Thesis (Ph.D.)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
37 INORGANIC
ORGANIC
PHYSICAL AND ANALYTICAL CHEMISTRY
FLUOROURACILS
CONFORMATIONAL CHANGES
MOLECULAR STRUCTURE
PHOTOCHEMICAL REACTIONS
ADDUCTS
CYCLOALKANES
FLEXIBILITY
MOLECULAR BIOLOGY
STEREOCHEMISTRY
ULTRAVIOLET RADIATION
ALKANES
ANTIMETABOLITES
AZINES
CHEMICAL REACTIONS
DRUGS
ELECTROMAGNETIC RADIATION
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
MECHANICAL PROPERTIES
ORGANIC COMPOUNDS
ORGANIC FLUORINE COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PYRIMIDINES
RADIATIONS
TENSILE PROPERTIES
URACILS
550200* - Biochemistry
400500 - Photochemistry