Conformation-Specific Recognition of Carcinogen−DNA Adduct in Escherichia coli Nucleotide Excision Repair

We report a systematic and quantitative structure-function relationship study of the major N-[deoxyguanosin-8-yl]-2-aminofluorene adduct (AF) derived from the prototype carcinogen 2-aminofluorene and its derivatives. The AF adduct is known to exist in two distinct conformational motifs, depending upon the location of the hydrophobic fluorine moiety: major groove binding "B type" (B) conformation (AF-dG anti ) and base-displaced "stacked" (S) conformation (AF-dG syn ). The AF-induced S/B conformational heterogeneity is sequence-dependent and follows a typical two-site dynamic chemical exchange. The population of S conformation decreases in the order of 3'-G > A » C > T, indicating the importance of the purine flanking bases in promoting the stacking structure. Line-shape analysis showed that the S/B interconversion energy barriers (ΔG ‡ ) are in the narrow 14-16 kcal/mol range. The energy differences of the two conformers are relatively small (