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PDBsum entry 2hkc
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References listed in PDB file
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Key reference
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Title
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Base-Displaced intercalated structure of the food mutagen 2-Amino-3-Methylimidazo[4,5-F]quinoline in the recognition sequence of the nari restriction enzyme, A hotspot for -2 bp deletions.
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Authors
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F.Wang,
N.E.Demuro,
C.E.Elmquist,
J.S.Stover,
C.J.Rizzo,
M.P.Stone.
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Ref.
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J Am Chem Soc, 2006,
128,
10085-10095.
[DOI no: ]
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PubMed id
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Abstract
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The solution structure of the oligodeoxynucleotide
5'-d(CTCGGCXCCATC)-3'.5'-d(GATGGCGCCGAG)-3' containing the heterocyclic amine
8-[(3-methyl-3H-imidazo[4,5-f]quinolin-2-yl)amino]-2'-deoxyguanosine adduct (IQ)
at the third guanine in the NarI restriction sequence, a hot spot for -2 bp
frameshifts, is reported. Molecular dynamics calculations restrained by
distances derived from 24 (1)H NOEs between IQ and DNA, and torsion angles
derived from (3)J couplings, yielded ensembles of structures in which the
adducted guanine was displaced into the major groove with its glycosyl torsion
angle in the syn conformation. One proton of its exocyclic amine was
approximately 2.8 A from an oxygen of the 5' phosphodiester linkage, suggesting
formation of a hydrogen bond. The carcinogen-guanine linkage was defined by
torsion angles alpha' [N9-C8-N(IQ)-C2(IQ)] of 159 +/- 7 degrees and beta'
[C8-N(IQ)-C2(IQ)-N3(IQ)] of -23 +/- 8 degrees . The complementary cytosine was
also displaced into the major groove. This allowed IQ to intercalate between the
flanking C.G base pairs. The disruption of Watson-Crick hydrogen bonding was
corroborated by chemical-shift perturbations for base aromatic protons in the
complementary strand opposite to the modified guanine. Chemical-shift
perturbations were also observed for (31)P resonances corresponding to
phosphodiester linkages flanking the adduct. The results confirmed that IQ
adopted a base-displaced intercalated conformation in this sequence context but
did not corroborate the formation of a hydrogen bond between the IQ quinoline
nitrogen and the complementary dC [Elmquist, C. E.; Stover, J. S.; Wang, Z.;
Rizzo, C. J. J. Am. Chem. Soc. 2004, 126, 11189-11201].
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Headers
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