4HQI

Structure of O6-Benzyl-2'-deoxyguanosine opposite perimidinone-derived synthetic nucleoside in DNA duplex

4HQI の概要

• エントリーDOI: 10.2210/pdb4hqi/pdb
• 分子名称: Short modified nucleic acids, SPERMINE, STRONTIUM ION, ... (4 entities in total)
• 機能のキーワード: b-form dna, o6-benzyl-2'-deoxyguanosine, dper, perimidinone-derived nucleoside, dickerson-drew dodecamer, dna
• 由来する生物種: SYNTHETIC CONSTRUCT
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 7943.17

構造登録者

Kowal, E.A.,Lad, R.,Pallan, P.S.,Muffly, E.,Wawrzak, Z.,Egli, M.,Sturla, S.J.,Stone, M.P. (登録日: 2012-10-25, 公開日: 2013-07-10, 最終更新日: 2024-02-28)

主引用文献

Kowal, E.A.,Lad, R.R.,Pallan, P.S.,Dhummakupt, E.,Wawrzak, Z.,Egli, M.,Sturla, S.J.,Stone, M.P.
Recognition of O6-benzyl-2'-deoxyguanosine by a perimidinone-derived synthetic nucleoside: a DNA interstrand stacking interaction.
Nucleic Acids Res., 41:7566-7576, 2013

PubMed Abstract: The 2'-deoxynucleoside containing the synthetic base 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1H-perimidin-2(3H)-one] (dPer) recognizes in DNA the O(6)-benzyl-2'-deoxyguanosine nucleoside (O(6)-Bn-dG), formed by exposure to N-benzylmethylnitrosamine. Herein, we show how dPer distinguishes between O(6)-Bn-dG and dG in DNA. The structure of the modified Dickerson-Drew dodecamer (DDD) in which guanine at position G(4) has been replaced by O(6)-Bn-dG and cytosine C(9) has been replaced with dPer to form the modified O(6)-Bn-dG:dPer (DDD-XY) duplex [5'-d(C(1)G(2)C(3)X(4)A(5)A(6)T(7)T(8)Y(9)G(10)C(11)G(12))-3']2 (X = O(6)-Bn-dG, Y = dPer) reveals that dPer intercalates into the duplex and adopts the syn conformation about the glycosyl bond. This provides a binding pocket that allows the benzyl group of O(6)-Bn-dG to intercalate between Per and thymine of the 3'-neighbor A:T base pair. Nuclear magnetic resonance data suggest that a similar intercalative recognition mechanism applies in this sequence in solution. However, in solution, the benzyl ring of O(6)-Bn-dG undergoes rotation on the nuclear magnetic resonance time scale. In contrast, the structure of the modified DDD in which cytosine at position C(9) is replaced with dPer to form the dG:dPer (DDD-GY) [5'-d(C(1)G(2)C(3)G(4)A(5)A(6)T(7)T(8)Y(9)G(10)C(11)G(12))-3']2 duplex (Y = dPer) reveals that dPer adopts the anti conformation about the glycosyl bond and forms a less stable wobble pairing interaction with guanine.

PubMed: 23748954
DOI: 10.1093/nar/gkt488

実験手法

X-RAY DIFFRACTION (1.7 Å)