6IA4

Human telomeric G-quadruplex with 8-oxo-G substitution in the outer G-quartet

6IA4 の概要

• エントリーDOI: 10.2210/pdb6ia4/pdb
• NMR情報: BMRB: 34332
• 分子名称: hTel-oxoG21 (1 entity in total)
• 機能のキーワード: human telomere, oxidative stress, g-quadruplex, nmr., dna
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7607.88

構造登録者

Bielskute, S.,Plavec, J.,Podbevsek, P. (登録日: 2018-11-26, 公開日: 2019-01-30, 最終更新日: 2024-06-19)

主引用文献

Bielskute, S.,Plavec, J.,Podbevsek, P.
Impact of Oxidative Lesions on the Human Telomeric G-Quadruplex.
J. Am. Chem. Soc., 141:2594-2603, 2019

PubMed Abstract: Telomere attrition is closely associated with cell aging and exposure to reactive oxygen species (ROS). While oxidation products of nucleotides have been studied extensively in the past, the underlying secondary/tertiary structural changes in DNA remain poorly understood. In this work, we systematically probed guanine positions in the human telomeric oligonucleotide sequence (hTel) by substitutions with the major product of ROS, 8-oxo-7,8-dihydroguanine (G), and evaluated the G-quadruplex forming ability of such oligonucleotides. Due to reduced hydrogen-bonding capability caused by G, a loss of G-quadruplex structure was observed for most oligonucleotides containing oxidative lesions. However, some positions in the hTel sequence were found to tolerate substitutions with G. Due to G's preference for the syn conformation, distinct responses were observed when replacing guanines with different glycosidic conformations. Accommodation of G at sites originally in syn or anti in nonsubstituted hTel G-quadruplex requires a minor structural rearrangement or a major conformational shift, respectively. The system responds by retaining or switching to a fold where G is in syn conformation. Most importantly, these G-quadruplex structures are still stable at physiological temperatures and should be considered detrimental in higher-order telomere structures.

PubMed: 30657306
DOI: 10.1021/jacs.8b12748

実験手法

SOLUTION NMR