1U6N

Solution Structure of an Oligodeoxynucleotide Containing a Butadiene Derived N1 b-Hydroxyalkyl Adduct on Deoxyinosine in the Human N-ras Codon 61 Sequence

1U6N の概要

• エントリーDOI: 10.2210/pdb1u6n/pdb
• 関連するPDBエントリー: 1U6O
• 分子名称: 5'-D(*CP*GP*GP*AP*CP*(2BD)P*AP*GP*AP*AP*G)-3', 5'-D(*CP*TP*TP*CP*TP*TP*GP*TP*CP*CP*G)-3' (2 entities in total)
• 機能のキーワード: butadiene, deoxyinosine, ras61, dna
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 6778.48

構造登録者

Scholdberg, T.A.,Merritt, W.K.,Dean, S.M.,Kowalcyzk, A.,Harris, T.M.,Harris, C.M.,Lloyd, R.S.,Stone, M.P. (登録日: 2004-07-30, 公開日: 2004-08-10, 最終更新日: 2024-05-22)

主引用文献

Scholdberg, T.A.,Merritt, W.K.,Dean, S.M.,Kowalcyzk, A.,Harris, C.M.,Harris, T.M.,Rizzo, C.J.,Lloyd, R.S.,Stone, M.P.
Structure of an Oligodeoxynucleotide Containing a Butadiene Oxide-Derived N1 Beta-Hydroxyalkyl Deoxyinosine Adduct in the Human N-ras Codon 61 Sequence.
Biochemistry, 44:3327-3337, 2005

PubMed Abstract: The solution structure of the N1-(1-hydroxy-3-buten-2(S)-yl)-2'-deoxyinosine adduct arising from the alkylation of adenine N1 by butadiene epoxide (BDO), followed by deamination to deoxyinosine, was determined, in the oligodeoxynucleotide d(CGGACXAGAAG).d(CTTCTCGTCCG). This oligodeoxynucleotide contained the BDO adduct at the second position of codon 61 of the human N-ras protooncogene, and was named the ras61 S-N1-BDO-(61,2) adduct. (1)H NMR revealed a weak C(5) H1' to X(6) H8 NOE, followed by an intense X(6) H8 to X(6) H1' NOE. Simultaneously, the X(6) H8 to X(6) H3' NOE was weak. The resonance arising from the T(17) imino proton was not observed. (1)H NOEs between the butadiene moiety and the DNA positioned the adduct in the major groove. Structural refinement based upon a total of 364 NOE-derived distance restraints yielded a structure in which the modified deoxyinosine was in the high syn conformation about the glycosyl bond, and T(17), the complementary nucleotide, was stacked into the helix, but not hydrogen bonded with the adducted inosine. The refined structure provided a plausible hypothesis as to why this N1 deoxyinosine adduct strongly coded for the incorporation of dCTP during trans lesion DNA replication, both in Escherichia coli [Rodriguez, D. A., Kowalczyk, A., Ward, J. B. J., Harris, C. M., Harris, T. M., and Lloyd, R. S. (2001) Environ. Mol. Mutagen. 38, 292-296], and in mammalian cells [Kanuri, M., Nechev, L. N., Tamura, P. J., Harris, C. M., Harris, T. M., and Lloyd, R. S. (2002) Chem. Res. Toxicol. 15, 1572-1580]. Rotation of the N1 deoxyinosine adduct into the high syn conformation may facilitate incorporation of dCTP via Hoogsteen-type templating with deoxyinosine, thus generating A-to-G mutations.

PubMed: 15736943
DOI: 10.1021/bi0482452

実験手法

SOLUTION NMR