1AX7

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

Summary for 1AX7

• Entry DOI: 10.2210/pdb1ax7/pdb
• Descriptor: DNA DUPLEX D(AAC-[AF]G-CTACCATCC)D(GGATGGTAG), 2-AMINOFLUORENE (3 entities in total)
• Functional Keywords: dna duplex, aminofluorene adduct, carcinogen adduct, template-primer junction, dna
• Total number of polymer chains: 2
• Total formula weight: 6897.66

Authors

Mao, B.,Gu, Z.,Gorin, A.A.,Hingerty, B.E.,Broyde, S.,Patel, D.J. (deposition date: 1997-10-30, release date: 1998-07-01, Last modification date: 2024-05-22)

Primary citation

Mao, B.,Gu, Z.,Gorin, A.,Hingerty, B.E.,Broyde, S.,Patel, D.J.
Solution structure of the aminofluorene-stacked conformer of the syn [AF]-C8-dG adduct positioned at a template-primer junction.
Biochemistry, 36:14491-14501, 1997

PubMed Abstract: 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.

PubMed: 9398168
DOI: 10.1021/bi972206r

Experimental method

SOLUTION NMR