1djd
THE SOLUTION STRUCTURE OF A NON-BAY REGION 11R-BENZ[A]ANTHRACENE OXIDE ADDUCT AT THE N6 POSITION OF ADENINE OF AN OLIGODEOXYNUCLEOTIDE CONTAINING THE HUMAN N-RAS CODON 61 SEQUENCE
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OverviewOverview
The structure of the non-bay region (8S,9R,10S,11R)-N(6)-[11-(8,9,10, 11-tetrahydro-8,9,10-trihydroxybenz[a]anthracenyl)]-2'-de oxyadenosyl, adduct at X(6) of 5'-d(CGGACXAGAAG)-3'.5'-d(CTTCTTGTCCG)-3', incorporating, codons 60, 61 (underlined), and 62 of the human N-ras protooncogene, was, determined. Molecular dynamics simulations were restrained by 475 NOEs, from (1)H NMR. The benz[a]anthracene moiety intercalated above the 5'-face, of the modified base pair and from the major groove. The duplex suffered, distortion at and immediately adjacent to the adduct site. This was, evidenced by the disruption of the Watson-Crick base pairing for X(6) x, T(17) and A(7) x T(16) and the increased rise of 7.7 A between base pairs, C(5) x G(18) and X(6) x T(17). Increased disorder was observed as excess, line width of proton resonances near the lesion site. Comparison with the, bay region benzo[a]pyrene [Zegar, I. S., Kim, S. J., Johansen, T. N., Horton, P. J., Harris, C. M., Harris, T. M., and Stone, M. P. (1996), Biochemistry 35, 6212-6224] and bay region benz[a]anthracene [Li, Z., Mao, H., Kim, H.-Y., Tamura, P. J., Harris, C. M., Harris, T. M., and Stone, M., P. (1999) Biochemistry 38, 2969-2981] adducts with the corresponding, stereochemistry and at the same site shows that this non-bay region, benz[a]anthracene lesion assumes different base pair geometry, in addition, to exhibiting greater disorder. These differences are attributed to the, loss of the bay region ring. The results suggest the bay region ring, contributes to base stacking interactions at the lesion site. These, structural differences between the non-bay and bay region lesions are, correlated with site-specific mutagenesis data. The bay region, benzo[a]pyrene and bay region benz[a]anthracene adducts were poorly, replicated in vivo, and induced A --> G mutations. In contrast, the, non-bay region benz[a]anthracene adduct was easily bypassed in vivo and, was nonmutagenic.
About this StructureAbout this Structure
1DJD is a Protein complex structure of sequences from [1] with TBT as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Role of a polycyclic aromatic hydrocarbon bay region ring in modulating DNA adduct structure: the non-bay region (8S,9R,10S, 11R)-N(6)-[11-(8,9,10,11-tetrahydro-8,9, 10-trihydroxybenz[a]anthracenyl)]-2'-deoxyadenosyl adduct in codon 61 of the human N-ras protooncogene., Li Z, Kim HY, Tamura PJ, Harris CM, Harris TM, Stone MP, Biochemistry. 1999 Nov 9;38(45):14820-32. PMID:10555964 [[Category: benz[a]anthracene-dna duplex]]
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