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DNA Sequence Modulates the Conformation of the Food Mutagen 2-Amino-3-methylimidazo[4,5-f]quinoline in the Recognition Sequence of the NarI Restriction Enzyme.

Authors :
Feng Wang
Elmquist, C. Eric
Stover, James S.
Rizzo, Carmelo J.
Stone, Michael P.
Source :
Biochemistry. 7/24/2007, Vol. 46 Issue 29, p8498-8516. 19p. 3 Diagrams, 2 Charts, 8 Graphs.
Publication Year :
2007

Abstract

The conformations of C8-dG adducts of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) positioned in the C-X¹-G, G-X²-C, and C-X³-C contexts in the C-G¹-G²-C-G³-C-C recognition sequence of the Nan restriction enzyme were compared, using the oligodeoxynucleotides 5′-d(CTCXGCGCCATC)-3′5′-d(GATGGCGCCGAG)-3′, 5′-d(CTCGXCGCCATC)-3′5′-d(GATGGCGCCGAG)-3′, and 5′- d(CTCGGCXCCATC)-3′·5′-d(GATGGCGCCGAG)-3′ (X is the C8-dG adduct of IQ). These were the NarIIQ1, NarIIQ2, and NarIIQ3 duplexes, respectively. In each instance, the glycosyl torsion angle x for the IQ-modified dG was in the syn conformation. The orientations of the IQ moieties were dependent upon the conformations of torsion angles α′ [N9-C8-N(IQ)-C2(IQ)] and β′ [C8-N(IQ)-C2(IQ)-N3(IQ)I, which were monitored by the patterns of ¹H NOEs between the IQ moieties and the DNA in the three sequence contexts. The conformational states of IQ torsion angles β′ and β′ were predicted from the refined structures of the three adducts obtained from restrained molecular dynamics calculations, utilizing simulated annealing protocols. For the NarIIQ1 and NarIIQ2 duplexes, the β′ torsion angles were predicted to be -176 ± 8° and -160 ± 8°, respectively, whereas for the NarIIQ3 duplex, torsion angle β′ was predicted to be 159 ± 7°. Likewise, for the NarIIQ1 and NarIIQ2 duplexes, the β′ torsion angles were predicted to be -152 + 8° and -164 ± 7°, respectively, whereas for the NarIIQ3 duplex, torsion angle β′ was predicted to be -23 ± 8°. Consequently, the conformations of the IQ adduct in the NarIIQ1 and NarIIQ2 duplexes were similar, with the IQ methyl protons and IQ H4 and H5 protons facing outward in the minor groove, whereas in the NarIIQ3 duplex, the IQ methyl protons and the IQ H4 and H5 protons faced into the DNA duplex, facilitating the base-displaced intercalated orientation of the IQ moiety [Wang, F., Elmquist, C. E., Stover, J. S., Rizzo, C. J., and Stone, M. P. (2006) J. Am. Chem. Soc. 128, 10085- 10095]. In contrast, for the NarIIQ1 and NarIIQ2 duplexes, the IQ moiety remained in the minor groove. These sequence-dependent differences suggest that base-displaced intercalation of the IQ adduct is favored when both the 5′- and 3′-flanking nucleotides in the complementary strand are guanines. These conformational differences may correlate with sequence-dependent differences in translesion replication. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00062960
Volume :
46
Issue :
29
Database :
Academic Search Index
Journal :
Biochemistry
Publication Type :
Academic Journal
Accession number :
25929695
Full Text :
https://doi.org/10.1021/bi700361u