2KAS

HNE-dG adduct mismatched with dA in basic solution

2KAS の概要

• エントリーDOI: 10.2210/pdb2kas/pdb
• 関連するPDBエントリー: 2KAR
• 分子名称: 5'-D(*DGP*DCP*DTP*DAP*DGP*DCP*DGP*DAP*DGP*DTP*DCP*DC)-3', 5'-D(*DGP*DGP*DAP*DCP*DTP*DAP*DGP*DCP*DTP*DAP*DGP*DC)-3', (4S)-nonane-1,4-diol (3 entities in total)
• 機能のキーワード: hne-dg, mismatch, hydroxynonenal, dna
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7511.06

構造登録者

Huang, H.,Wang, H.,Lloyd, R.S.,Rizzo, C.J.,Stone, M.P. (登録日: 2008-11-13, 公開日: 2009-05-26, 最終更新日: 2024-05-22)

主引用文献

Huang, H.,Wang, H.,Lloyd, R.S.,Rizzo, C.J.,Stone, M.P.
Conformational interconversion of the trans-4-hydroxynonenal-derived (6S,8R,11S) 1,N(2)-deoxyguanosine adduct when mismatched with deoxyadenosine in DNA
Chem.Res.Toxicol., 22:187-200, 2009

PubMed Abstract: The (6S,8R,11S) 1,N(2)-HNE-dGuo adduct of trans-4-hydroxynonenal (HNE) was incorporated into the duplex 5'-d(GCTAGCXAGTCC)-3'.5'-d(GGACTAGCTAGC)-3' [X = (6S,8R,11S) HNE-dG], in which the lesion was mismatched opposite dAdo. The (6S,8R,11S) adduct maintained the ring-closed 1,N(2)-HNE-dG structure. This was in contrast to when this adduct was correctly paired with dCyd, conditions under which it underwent ring opening and rearrangement to diastereomeric minor groove cyclic hemiacetals [ Huang , H. , Wang , H. , Qi , N. , Lloyd , R. S. , Harris , T. M. , Rizzo , C. J. , and Stone , M. P. ( 2008 ) J. Am. Chem. Soc. 130 , 10898 - 10906 ]. The (6S,8R,11S) adduct exhibited a syn/anti conformational equilibrium about the glycosyl bond. The syn conformation was predominant in acidic solution. Structural analysis of the syn conformation revealed that X(7) formed a distorted base pair with the complementary protonated A(18). The HNE moiety was located in the major groove. Structural perturbations were observed at the neighbor C(6).G(19) and A(8).T(17) base pairs. At basic pH, the anti conformation of X(7) was the major species. The 1,N(2)-HNE-dG intercalated and displaced the complementary A(18) in the 5'-direction, resulting in a bulge at the X(7).A(18) base pair. The HNE aliphatic chain was oriented toward the minor groove. The Watson-Crick hydrogen bonding of the neighboring A(8).T(17) base pair was also disrupted.

PubMed: 19053179
DOI: 10.1021/tx800320m

実験手法

SOLUTION NMR