1ax7

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SOLUTION STRUCTURE OF THE [AF]-C8-DG ADDUCT POSITIONED AT A TEMPLATE-PRIMER JUNCTION, NMR, 6 STRUCTURES

Overview

A solution structural study has been undertaken on the aminofluorene-C8-dG, ([AF]dG) adduct located at a single strand-double strand, d(A1-A2-C3-[AF]G4-C5-T6-A7-C8-C9-A10-T11-C12-C13).d, (G14-G15-A16-T17-G18-G19-T20-A 21-G22) 13/9-mer junction (designated, [AF]dG 13/9-mer) using proton-proton distance and intensity restraints, derived from NMR data in combination with a computational protocol, which, includes intensity refinement. This single strand-double strand junction, models one arm of a replication fork composed of a 13-mer template strand, which contains the [AF]dG modification site, and a 9-mer primer strand, which has been elongated up to, but not including, the modified guanine., The NMR data establish that the duplex segment retains a minimally, perturbed B-DNA conformation including Watson-Crick hydrogen-bonding at, the junctional dC5.dG22 base pair. The NMR spectra are consistent with the, guanine ring of the [AF]dG4 adduct adopting a syn glycosidic torsion angle, and being displaced into the major groove with the adjacent dC3 residue, displaced into the minor groove. Such a base displacement of the modified, guanine is accompanied by stacking of one face of the fluorene ring of, [AF]dG4 with the dC5.dG22 base pair, while the other face of the flourene, ring is stacked with the purine ring of the nonadjacent dA2 residue in the, intensity-refined solution structures of the [AF]dG 13/9-mer. A comparison, of structural features of the C8-[AF]dG adduct (this study) with those of, the (+)-trans-anti-N2-[BP]dG adduct [Cosman et al. (1995) Biochemistry 34, 15334-15350] in the same 13/9-mer junctional sequence context has, identified common features associated with the alignment of the modified, guanine adducts at the template-primer junction. Thus, despite differences, in the covalent linkage site for the C8-[AF]dG and, (+)-trans-anti-N2-[BP]dG adducts, one face of the aromatic ring of the, carcinogen stacks over the junctional base pair and in so doing displaces, the modified guanine in a syn alignment into the major groove. These, results lend credence to earlier proposals that such an adduct alignment, may represent a common mutagenic conformer at a template-primer junction, associated with a replication fork.

About this Structure

1AX7 is a Protein complex structure of sequences from [1] with AF as ligand. Full crystallographic information is available from OCA.

Reference

Solution structure of the aminofluorene-stacked conformer of the syn [AF]-C8-dG adduct positioned at a template-primer junction., Mao B, Gu Z, Gorin A, Hingerty BE, Broyde S, Patel DJ, Biochemistry. 1997 Nov 25;36(47):14491-501. PMID:9398168

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