NMR studies of the exocyclic 1,N sub 6 -ethenodeoxyadenosine adduct (. epsilon. dA) opposite thymidine in a DNA duplex. Nonplanar alignment of. epsilon. dA(anti) and dT(anti) at the lesion site

Journal Article · Tue Feb 19 00:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00221a014· OSTI ID:5398847

Kouchakdjian, M; Patel, D J ^[1]; Eisenberg, M ^[2]; Yarema, K; Basu, A; Essigmann, J ^[3]

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1. Columbia Univ., New York, NY (USA)
2. State Univ. of New York, Stony Brook (USA)
3. Massachusetts Inst. of Tech., Cambridge (USA)

Two-dimensional proton NMR studies are reported on the complementary d(C-A-T-G-T-G-T-A-C){center dot}d(G-T-A-C-{epsilon}A-C-A-T-G) nonanucleotide duplex (designated {epsilon}dA{center dot}dT 9-mer duplex) containing 1,N{sup 6}-ethenodeoxyadenosine ({epsilon}dA), a carcinogen-DNA adduct, positioned opposite thymidine in the center of the helix. The authors NMR studies have focused on the conformation of the {epsilon}dA{center dot}dT 9-mer duplex at neutral pH with emphasis on defining the alignment at the dT5{center dot}{epsilon}dA14 lesion site. The through-space NOE distance connectivities establish that both dT5 and {epsilon}dA14 adopt anti glycosidic torsion angles, are directed into the interior of the helix, and stack with flanking Watson-Crick dG4{center dot}dC15 and dG6{center dot}dC13 pairs. Furthermore, the d(G4-T5-G6){center dot}d(C13-{epsilon}A14-C15) trinucleotide segment centered about the dT5{center dot}{epsilon}dA14 lesion site adopts a right-handed helical conformation in solution. Energy minimization computations were undertaken starting from six different alignments of dT5(anti) and {epsilon}dA14(anti) at the lesion site and were guided by distance constraints defined by lower and upper bounds estimated from NOESY data sets on the {epsilon}dA{center dot}dT 9-mer duplex. The NMR data are consistent with a nonplanar alignment of {epsilon}dA14(anti) and dT5(anti) with dT5 displaced toward the flanking dG4{center dot}dC15 base pair within the d(G4-T5-G6){center dot}d(C13-{epsilon}A14-C15) segment of the {epsilon}dA{center dot}dT 9-mer duplex.

• OSTI ID: 5398847
• Journal Information: Biochemistry; (United States), Vol. 30:7; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
DNA ADDUCTS
NUCLEAR MAGNETIC RESONANCE
EPOXIDES
BIOLOGICAL EFFECTS
MOLECULAR STRUCTURE
THYMIDINE
VINYL CHLORIDE
ADDUCTS
AZINES
CHLORINATED ALIPHATIC HYDROCARBONS
HALOGENATED ALIPHATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
MAGNETIC RESONANCE
NUCLEOSIDES
NUCLEOTIDES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PYRIMIDINES
RESONANCE
RIBOSIDES
550201* - Biochemistry- Tracer Techniques