1k29
From Proteopedia
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Solution Structure of a DNA Duplex Containing M1G Opposite a 2 Base Pair Deletion
Overview
The pyrimidopurinone adduct M1G, [3-(2'-deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-a]-purin-10(3H)-on, e], formed in DNA upon exposure to malondialdehyde or base propenals, was, incorporated into 5'-d(ATCGCMCGGCATG)-3'-5'-d(CATGCCGCGAT)-3', where M =, M1G. This duplex contained a two-nucleotide bulge in the modified strand, and was named the M1G-2BD oligodeoxynucleotide. It provided a model for -2, bp strand slippage deletions associated with the (CpG)3-iterated repeat, hotspot for frameshift mutations from the Salmonella typhimurium hisD3052, gene. M1G was chemically stable in the M1G-2BD duplex at neutral pH. The, two-base bulge in the M1G-2BD oligodeoxynucleotide was localized and, consisted of M1G and the 3'-neighbor deoxycytosine. The intrahelical, orientation of M1G was established from a combination of NOE and chemical, shift data. M1G was in the anti conformation about the glycosyl bond. The, 3'-neighbor deoxycytosine appeared to be extruded toward the major groove., In contrast, when M1G was placed into the corresponding fully, complementary (CpG)3-iterated repeat duplex at neutral pH, spontaneous and, quantitative ring-opening to N(2)-(3-oxo-1-propenyl)-dG (the OPG adduct), was facilitated [Mao, H., Reddy, G. R., Marnett, L. J., and Stone, M. P., (1999) Biochemistry 38, 13491-13501]. The structure of the M1G-2BD duplex, suggested that the bulged sequence lacked a cytosine amino group properly, positioned to facilitate opening of M1G and supports the notion that, proper positioning of deoxycytosine complementary to M1G is necessary to, promote ring-opening of the exocyclic adduct in duplex DNA. The structure, of the M1G-2BD duplex was similar to that of the structural analogue, 1,N(2)-propanodeoxyguanosine (PdG) in the corresponding PdG-2BD duplex, [Weisenseel, J. P., Moe, J. G., Reddy, G. R., Marnett, L. J., and Stone, M. P. (1995) Biochemistry 34, 50-64]. The fixed position of the bulged, bases in both instances suggests that these exocyclic adducts do not, facilitate transient bulge migration.
About this Structure
1K29 is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
The exocyclic 1,N2-deoxyguanosine pyrimidopurinone M1G is a chemically stable DNA adduct when placed opposite a two-base deletion in the (CpG)3 frameshift hotspot of the Salmonella typhimurium hisD3052 gene., Schnetz-Boutaud NC, Saleh S, Marnett LJ, Stone MP, Biochemistry. 2001 Dec 25;40(51):15638-49. PMID:11747439
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