Solution conformation of the (+)-trans-antibenzo[g]chrysene-dA adduct opposite dT in a DNA duplex

Asif K. Suri, Bing Mao, Shantu Amin, Nicholas Geacintov, Dinshaw J. Patel

Research output: Contribution to journalArticle

Abstract

The solution structure of the adduct derived from the covalent bonding of the fjord region (+)-(11S, 12R, 13R, 14S) stereoisomer of anti-11,12-dihydroxy-13,14-epoxy-11 12,13,14-tetrahydrobenzo[g]chrysene, (+)-anti-B[g]CDE, to the exocyclic N6 amino group of the adenine residue dA6, (designated (+)-trans-anti-(B[g]C)dA6), positioned opposite a thymine residue dT17 in the DNA sequence context d(C1-T2-C3-T4-C5-(B[g]C)A6-C7-T8-T9-C 10-C11)· d(G12-G13-A14-A15-G16-T17-G18-A19-G20-A21-G22) (designated (B[g]C)dA·dT 11-mer duplex), has been studied using structural information derived from NMR data in combination with molecular dynamics (MD) calculations. The solution structure of the (+)trans-anti(B[g]C)dA·dT 11-mer duplex has been determined using an MD protocol where both interproton distance and dihedral angle restraints deduced from NOESY and COSY spectra are used during the refinement process, followed by additional relaxation matrix refinement to the observed NOESY intensities to account for spin diffusion effects. The results established that the covalently attached benzo[g]chrysene ring intercalates into the DNA helix directed towards the 5'-side of the modified strand and stacks predominantly with dT17 when intercalated between dC5·dG18 and (B[g]C)dA6·dT17 base-pairs. All base-pairs, including the modified (B[g]C)dA6· dT17 base-pair, are aligned through Watson-Crick pairing as in normal B-DNA. In addition, the potential strain associated with the highly sterically hindered fjord region of the aromatic portion of the benzo[g]chrysenyl ring is relieved through the adoption of a non-planar, propeller-like geometry within the chrysenyl ring system. This conformation shares common structural features with the related (+)-trans-anti(B[c]Ph)dA adduct in the identical base sequence context, derived from the fjord region (+)-(1S,2R,3R,4S)-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahy- drobenzo[c]phenanthrene stereoisomer, in which intercalation is also observed towards the 5'-side of the modified dA6 dT17 base-pair.

Original languageEnglish (US)
Pages (from-to)289-307
Number of pages19
JournalJournal of Molecular Biology
Volume292
Issue number2
DOIs
StatePublished - Sep 17 1999

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Base Pairing
Estuaries
Stereoisomerism
DNA
Molecular Dynamics Simulation
B-Form DNA
Thymine
Adenine
chrysene

Keywords

  • 'Fjord' region covalent polycyclic aromatic hydrocarbon (PAH)-N-adenine adducts
  • Absolute configuration defines the directionality of carcinogen alignment
  • Carcinogen intercalation without base displacement
  • Non-planarity of PAH ring at intercalation site

ASJC Scopus subject areas

  • Virology

Cite this

Solution conformation of the (+)-trans-antibenzo[g]chrysene-dA adduct opposite dT in a DNA duplex. / Suri, Asif K.; Mao, Bing; Amin, Shantu; Geacintov, Nicholas; Patel, Dinshaw J.

In: Journal of Molecular Biology, Vol. 292, No. 2, 17.09.1999, p. 289-307.

Research output: Contribution to journalArticle

Suri, Asif K. ; Mao, Bing ; Amin, Shantu ; Geacintov, Nicholas ; Patel, Dinshaw J. / Solution conformation of the (+)-trans-antibenzo[g]chrysene-dA adduct opposite dT in a DNA duplex. In: Journal of Molecular Biology. 1999 ; Vol. 292, No. 2. pp. 289-307.
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title = "Solution conformation of the (+)-trans-antibenzo[g]chrysene-dA adduct opposite dT in a DNA duplex",
abstract = "The solution structure of the adduct derived from the covalent bonding of the fjord region (+)-(11S, 12R, 13R, 14S) stereoisomer of anti-11,12-dihydroxy-13,14-epoxy-11 12,13,14-tetrahydrobenzo[g]chrysene, (+)-anti-B[g]CDE, to the exocyclic N6 amino group of the adenine residue dA6, (designated (+)-trans-anti-(B[g]C)dA6), positioned opposite a thymine residue dT17 in the DNA sequence context d(C1-T2-C3-T4-C5-(B[g]C)A6-C7-T8-T9-C 10-C11)· d(G12-G13-A14-A15-G16-T17-G18-A19-G20-A21-G22) (designated (B[g]C)dA·dT 11-mer duplex), has been studied using structural information derived from NMR data in combination with molecular dynamics (MD) calculations. The solution structure of the (+)trans-anti(B[g]C)dA·dT 11-mer duplex has been determined using an MD protocol where both interproton distance and dihedral angle restraints deduced from NOESY and COSY spectra are used during the refinement process, followed by additional relaxation matrix refinement to the observed NOESY intensities to account for spin diffusion effects. The results established that the covalently attached benzo[g]chrysene ring intercalates into the DNA helix directed towards the 5'-side of the modified strand and stacks predominantly with dT17 when intercalated between dC5·dG18 and (B[g]C)dA6·dT17 base-pairs. All base-pairs, including the modified (B[g]C)dA6· dT17 base-pair, are aligned through Watson-Crick pairing as in normal B-DNA. In addition, the potential strain associated with the highly sterically hindered fjord region of the aromatic portion of the benzo[g]chrysenyl ring is relieved through the adoption of a non-planar, propeller-like geometry within the chrysenyl ring system. This conformation shares common structural features with the related (+)-trans-anti(B[c]Ph)dA adduct in the identical base sequence context, derived from the fjord region (+)-(1S,2R,3R,4S)-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahy- drobenzo[c]phenanthrene stereoisomer, in which intercalation is also observed towards the 5'-side of the modified dA6 dT17 base-pair.",
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T1 - Solution conformation of the (+)-trans-antibenzo[g]chrysene-dA adduct opposite dT in a DNA duplex

AU - Suri, Asif K.

AU - Mao, Bing

AU - Amin, Shantu

AU - Geacintov, Nicholas

AU - Patel, Dinshaw J.

PY - 1999/9/17

Y1 - 1999/9/17

N2 - The solution structure of the adduct derived from the covalent bonding of the fjord region (+)-(11S, 12R, 13R, 14S) stereoisomer of anti-11,12-dihydroxy-13,14-epoxy-11 12,13,14-tetrahydrobenzo[g]chrysene, (+)-anti-B[g]CDE, to the exocyclic N6 amino group of the adenine residue dA6, (designated (+)-trans-anti-(B[g]C)dA6), positioned opposite a thymine residue dT17 in the DNA sequence context d(C1-T2-C3-T4-C5-(B[g]C)A6-C7-T8-T9-C 10-C11)· d(G12-G13-A14-A15-G16-T17-G18-A19-G20-A21-G22) (designated (B[g]C)dA·dT 11-mer duplex), has been studied using structural information derived from NMR data in combination with molecular dynamics (MD) calculations. The solution structure of the (+)trans-anti(B[g]C)dA·dT 11-mer duplex has been determined using an MD protocol where both interproton distance and dihedral angle restraints deduced from NOESY and COSY spectra are used during the refinement process, followed by additional relaxation matrix refinement to the observed NOESY intensities to account for spin diffusion effects. The results established that the covalently attached benzo[g]chrysene ring intercalates into the DNA helix directed towards the 5'-side of the modified strand and stacks predominantly with dT17 when intercalated between dC5·dG18 and (B[g]C)dA6·dT17 base-pairs. All base-pairs, including the modified (B[g]C)dA6· dT17 base-pair, are aligned through Watson-Crick pairing as in normal B-DNA. In addition, the potential strain associated with the highly sterically hindered fjord region of the aromatic portion of the benzo[g]chrysenyl ring is relieved through the adoption of a non-planar, propeller-like geometry within the chrysenyl ring system. This conformation shares common structural features with the related (+)-trans-anti(B[c]Ph)dA adduct in the identical base sequence context, derived from the fjord region (+)-(1S,2R,3R,4S)-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahy- drobenzo[c]phenanthrene stereoisomer, in which intercalation is also observed towards the 5'-side of the modified dA6 dT17 base-pair.

AB - The solution structure of the adduct derived from the covalent bonding of the fjord region (+)-(11S, 12R, 13R, 14S) stereoisomer of anti-11,12-dihydroxy-13,14-epoxy-11 12,13,14-tetrahydrobenzo[g]chrysene, (+)-anti-B[g]CDE, to the exocyclic N6 amino group of the adenine residue dA6, (designated (+)-trans-anti-(B[g]C)dA6), positioned opposite a thymine residue dT17 in the DNA sequence context d(C1-T2-C3-T4-C5-(B[g]C)A6-C7-T8-T9-C 10-C11)· d(G12-G13-A14-A15-G16-T17-G18-A19-G20-A21-G22) (designated (B[g]C)dA·dT 11-mer duplex), has been studied using structural information derived from NMR data in combination with molecular dynamics (MD) calculations. The solution structure of the (+)trans-anti(B[g]C)dA·dT 11-mer duplex has been determined using an MD protocol where both interproton distance and dihedral angle restraints deduced from NOESY and COSY spectra are used during the refinement process, followed by additional relaxation matrix refinement to the observed NOESY intensities to account for spin diffusion effects. The results established that the covalently attached benzo[g]chrysene ring intercalates into the DNA helix directed towards the 5'-side of the modified strand and stacks predominantly with dT17 when intercalated between dC5·dG18 and (B[g]C)dA6·dT17 base-pairs. All base-pairs, including the modified (B[g]C)dA6· dT17 base-pair, are aligned through Watson-Crick pairing as in normal B-DNA. In addition, the potential strain associated with the highly sterically hindered fjord region of the aromatic portion of the benzo[g]chrysenyl ring is relieved through the adoption of a non-planar, propeller-like geometry within the chrysenyl ring system. This conformation shares common structural features with the related (+)-trans-anti(B[c]Ph)dA adduct in the identical base sequence context, derived from the fjord region (+)-(1S,2R,3R,4S)-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahy- drobenzo[c]phenanthrene stereoisomer, in which intercalation is also observed towards the 5'-side of the modified dA6 dT17 base-pair.

KW - 'Fjord' region covalent polycyclic aromatic hydrocarbon (PAH)-N-adenine adducts

KW - Absolute configuration defines the directionality of carcinogen alignment

KW - Carcinogen intercalation without base displacement

KW - Non-planarity of PAH ring at intercalation site

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