Solution structure of the aminofluorene [AF]-intercalated conformer of the syn-[AF]-C8-dG adduct opposite dC in a DNA duplex

Bing Mao, Brian E. Hingerty, Suse Broyde, Dinshaw J. Patel

Research output: Contribution to journalArticle

Abstract

We report below on a conformational equilibrium between AF-intercalated and AF-external states in slow exchange for the [AF]dG lesion positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The slow exchange between states is attributed to interconversion between syn glycosidic torsion angle in the AF-intercalated and anti torsion angle in AF-external conformers of the [AF]dG opposite dC containing duplex. The present paper describes an NMR-molecular mechanics study that defines the solution structure of the AF-intercalated conformer for the case of [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The structure is of the base displacement-intercalation type where the aminofluorene ring is intercalated into the helix between intact Watson- Crick dG·dC base pairs, which results in a displacement of the modified guanine ring into the major groove where it stacks with the major groove edge of its 5'-flanking cytosine in the adduct duplex. The conformational equilibrium between AF-intercalated conformer (~70%) with a syn alignment and AF-external conformer (~30%) with an anti alignment for the [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context can be contrasted with our earlier demonstration that the population is 100% for the AP-intercalated conformer with a syn alignment at the N- (deoxyguanosin-8-yl)-2-aminopyrene ([AP]dG) adduct site positioned opposite dC in the same sequence context [Mao, B., Vyas, R. R., Hingerty, B. E., Broyde, S., Basu, A. K., and Patel, D. J. (1996) Biochemistry, 35, 12659- 12670]. This shift in population may reflect the much larger size of the pyrenyl ring of the [AP]dG adduct compared to the fluorenyl ring of the [AF]dG adduct which in turn might provide for a greater overlap of the aromatic amine with the flanking base pairs in the intercalated conformer of the former adduct in DNA.

Original languageEnglish (US)
Pages (from-to)81-94
Number of pages14
JournalBiochemistry
Volume37
Issue number1
DOIs
StatePublished - Jan 6 1998

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Dilatation and Curettage
DNA
Torsional stress
Base Pairing
Biochemistry
Molecular mechanics
Cytosine
Guanine
Intercalation
Amines
Demonstrations
DNA Adducts
Nuclear magnetic resonance
Mechanics
Population
N-(deoxyguanosin-8-yl)-2-aminofluorene

ASJC Scopus subject areas

  • Biochemistry

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Solution structure of the aminofluorene [AF]-intercalated conformer of the syn-[AF]-C8-dG adduct opposite dC in a DNA duplex. / Mao, Bing; Hingerty, Brian E.; Broyde, Suse; Patel, Dinshaw J.

In: Biochemistry, Vol. 37, No. 1, 06.01.1998, p. 81-94.

Research output: Contribution to journalArticle

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abstract = "We report below on a conformational equilibrium between AF-intercalated and AF-external states in slow exchange for the [AF]dG lesion positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The slow exchange between states is attributed to interconversion between syn glycosidic torsion angle in the AF-intercalated and anti torsion angle in AF-external conformers of the [AF]dG opposite dC containing duplex. The present paper describes an NMR-molecular mechanics study that defines the solution structure of the AF-intercalated conformer for the case of [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The structure is of the base displacement-intercalation type where the aminofluorene ring is intercalated into the helix between intact Watson- Crick dG·dC base pairs, which results in a displacement of the modified guanine ring into the major groove where it stacks with the major groove edge of its 5'-flanking cytosine in the adduct duplex. The conformational equilibrium between AF-intercalated conformer (~70{\%}) with a syn alignment and AF-external conformer (~30{\%}) with an anti alignment for the [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context can be contrasted with our earlier demonstration that the population is 100{\%} for the AP-intercalated conformer with a syn alignment at the N- (deoxyguanosin-8-yl)-2-aminopyrene ([AP]dG) adduct site positioned opposite dC in the same sequence context [Mao, B., Vyas, R. R., Hingerty, B. E., Broyde, S., Basu, A. K., and Patel, D. J. (1996) Biochemistry, 35, 12659- 12670]. This shift in population may reflect the much larger size of the pyrenyl ring of the [AP]dG adduct compared to the fluorenyl ring of the [AF]dG adduct which in turn might provide for a greater overlap of the aromatic amine with the flanking base pairs in the intercalated conformer of the former adduct in DNA.",
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N2 - We report below on a conformational equilibrium between AF-intercalated and AF-external states in slow exchange for the [AF]dG lesion positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The slow exchange between states is attributed to interconversion between syn glycosidic torsion angle in the AF-intercalated and anti torsion angle in AF-external conformers of the [AF]dG opposite dC containing duplex. The present paper describes an NMR-molecular mechanics study that defines the solution structure of the AF-intercalated conformer for the case of [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The structure is of the base displacement-intercalation type where the aminofluorene ring is intercalated into the helix between intact Watson- Crick dG·dC base pairs, which results in a displacement of the modified guanine ring into the major groove where it stacks with the major groove edge of its 5'-flanking cytosine in the adduct duplex. The conformational equilibrium between AF-intercalated conformer (~70%) with a syn alignment and AF-external conformer (~30%) with an anti alignment for the [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context can be contrasted with our earlier demonstration that the population is 100% for the AP-intercalated conformer with a syn alignment at the N- (deoxyguanosin-8-yl)-2-aminopyrene ([AP]dG) adduct site positioned opposite dC in the same sequence context [Mao, B., Vyas, R. R., Hingerty, B. E., Broyde, S., Basu, A. K., and Patel, D. J. (1996) Biochemistry, 35, 12659- 12670]. This shift in population may reflect the much larger size of the pyrenyl ring of the [AP]dG adduct compared to the fluorenyl ring of the [AF]dG adduct which in turn might provide for a greater overlap of the aromatic amine with the flanking base pairs in the intercalated conformer of the former adduct in DNA.

AB - We report below on a conformational equilibrium between AF-intercalated and AF-external states in slow exchange for the [AF]dG lesion positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The slow exchange between states is attributed to interconversion between syn glycosidic torsion angle in the AF-intercalated and anti torsion angle in AF-external conformers of the [AF]dG opposite dC containing duplex. The present paper describes an NMR-molecular mechanics study that defines the solution structure of the AF-intercalated conformer for the case of [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context. The structure is of the base displacement-intercalation type where the aminofluorene ring is intercalated into the helix between intact Watson- Crick dG·dC base pairs, which results in a displacement of the modified guanine ring into the major groove where it stacks with the major groove edge of its 5'-flanking cytosine in the adduct duplex. The conformational equilibrium between AF-intercalated conformer (~70%) with a syn alignment and AF-external conformer (~30%) with an anti alignment for the [AF]dG adduct positioned opposite dC in the d(C-[AF]G-C)·d(G-C-G) sequence context can be contrasted with our earlier demonstration that the population is 100% for the AP-intercalated conformer with a syn alignment at the N- (deoxyguanosin-8-yl)-2-aminopyrene ([AP]dG) adduct site positioned opposite dC in the same sequence context [Mao, B., Vyas, R. R., Hingerty, B. E., Broyde, S., Basu, A. K., and Patel, D. J. (1996) Biochemistry, 35, 12659- 12670]. This shift in population may reflect the much larger size of the pyrenyl ring of the [AP]dG adduct compared to the fluorenyl ring of the [AF]dG adduct which in turn might provide for a greater overlap of the aromatic amine with the flanking base pairs in the intercalated conformer of the former adduct in DNA.

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