Solution conformation of the (+)-trans-anti-[BP]dG adduct opposite a deletion site in a DNA duplex: Intercalation of the covalently attached benzo[a]pyrene into the helix with base displacement of the modified deoxyguanosine into the major groove Journal Article
| Authors: | Cosman, M.; Fiala, R.; Hingerty, B. E.; Amin, S.; Geacintov, N. E.; Broyde, S.; Patel, D. J. |
| Article Title: | Solution conformation of the (+)-trans-anti-[BP]dG adduct opposite a deletion site in a DNA duplex: Intercalation of the covalently attached benzo[a]pyrene into the helix with base displacement of the modified deoxyguanosine into the major groove |
| Abstract: | This paper reports on the solution structure of the (+)-trans-anti-[BP]dG adduct positioned opposite a deletion site in a DNA oligomer duplex which defines the alignment of this covalent benzo[a] pyrene-N2-deoxyguanosine stereoisomer relative to the deletion site. The combined NMR-molecular mechanics computation studies were undertaken on the (+)-trans-anti-[BP]dG adduct embedded in the d(C5-[BP]G6-C7)-d(G16–G17) sequence context in a duplex containing 11 residues on the modified strand and 10 on the partner, with no base opposite the modification. The exchangeable and nonexchangeable protons of the benzo [a] pyrenyl moiety and the nucleic acid were assigned following analysis of two-dimensional NMR data sets in H2O and D20 solution. The solution conformation of the (+)-trans-anti-[BP]dG.del 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by lower and upper bounds deduced from NOESY spectra as restraints in molecular mechanics computations in torsion angle space. The benzo[a]pyrene ring of [BP]dG6 is intercalated between intact Watson-Crick dC 5.dG 17 and dC7.dG 16 base pairs with the deoxyguanosine base of [BP] dG6 displaced into the major groove. The intercalation site is wedge shaped, being narrower toward the dG 16-dG 17 step on the deletion–containing strand. The deoxyguanosine base of [BP]dG6 which is positioned in the major groove is inclined relative to the helix axis and stacks over the 5′-flanking dC5 residue in the solution structure. The intercalative-base displacement structure of the (+)-tarns-anti-[BP]dG.del 11-mer duplex exhibits several unusually shifted proton resonances which can be readily accounted for by the ring current contribution of the deoxyguanosyl and pyrenyl rings of the [BP]dG6 adduct. This solution structure of the (+)-trans-anti-[BP]dG.del 11-mer duplex where the pyrene ring intercalates into the helix with displacement of the modified deoxyguanosine into the major groove strikingly contrasts with our previous study on the (+)-trans-anti-[BP]dG.dC 11-mer duplex [Cosman, M., et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1914–1918] where the benzo [a] pyrene ring is positioned in the minor groove without disruption of the Watson-Crick pairing at the [BP]dG.dC modification site. Thus, generation of the deletion site following removal of the dC opposite the (+)trans-anti-[BP]dG results in a displacement of the entire [BP]dG residue toward the major groove and intercalation of the benzo [a] pyrene ring into the helix. © 1994, American Chemical Society. All rights reserved. |
| Keywords: | sequence deletion; molecular sequence data; magnetic resonance spectroscopy; base sequence; deoxyguanosine; dna adduct; dna structure; benzo(a)pyrene; dna adducts; models, molecular; nucleic acid denaturation; protons; solutions; nucleic acid conformation; dna helix; structure analysis; carcinogens, environmental; dna conformation; intercalation complex; enantiomer; isomerism; intercalating agents; priority journal; article; benzo[a]pyrene derivative; support, u.s. gov't, p.h.s.; support, u.s. gov't, non-p.h.s.; deoxyguanosine derivative |
| Journal Title: | Biochemistry |
| Volume: | 33 |
| Issue: | 38 |
| ISSN: | 0006-2960 |
| Publisher: | American Chemical Society |
| Date Published: | 1994-09-27 |
| Start Page: | 11507 |
| End Page: | 11517 |
| Language: | English |
| DOI: | 10.1021/bi00204a013 |
| PROVIDER: | scopus |
| PUBMED: | 7918364 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work