3REI

2.65 Angstrom Crystal Structure of the Nucleosome Core Particle Assembled with a 145 bp Alpha-Satellite DNA (NCP145) Derivatized with Triamminechloroplatinum(II) Chloride

3REI の概要

• エントリーDOI: 10.2210/pdb3rei/pdb
• 関連するPDBエントリー: 1KX3 1KX4 1KX5 2NZD 3REH 3REJ 3REK 3REL
• 分子名称: Histone H3.2, Histone H4, Histone H2A type1, ... (9 entities in total)
• 機能のキーワード: nucleosome, structural protein-dna complex, structural protein/dna
• 由来する生物種: Xenopus laevis (clawed frog,common platanna,platanna); 詳細
• 細胞内の位置: Nucleus: P84233 P62799 P06897 P02281
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 207587.51

構造登録者

Wu, B.,Davey, C.A. (登録日: 2011-04-04, 公開日: 2012-03-14, 最終更新日: 2023-09-13)

主引用文献

Wu, B.,Davey, G.E.,Nazarov, A.A.,Dyson, P.J.,Davey, C.A.
Specific DNA structural attributes modulate platinum anticancer drug site selection and cross-link generation.
Nucleic Acids Res., 39:8200-8212, 2011

PubMed Abstract: Heavy metal compounds have toxic and medicinal potential through capacity to form strong specific bonds with macromolecules, and the interaction of platinum drugs at the major groove nitrogen atom of guanine bases primarily underlies their therapeutic activity. By crystallographic analysis of transition metal-and in particular platinum compound-DNA site selectivity in the nucleosome core, we establish that steric accessibility, which is controlled by specific structural parameters of the double helix, modulates initial guanine-metal bond formation. Moreover, DNA conformational features can be linked to both similarities and distinctions in platinum drug adduct formation between the naked and nucleosomal DNA states. Notably, structures that facilitate initial platinum-guanine bond formation can oppose cross-link generation, rationalizing the occurrence of long-lived therapeutically ineffective monofunctional adducts. These findings illuminate DNA structure-dependent reactivity and provide a novel framework for understanding metal-double helix interactions, which should facilitate the development of improved chromatin-targeting medicinal agents.

PubMed: 21724603
DOI: 10.1093/nar/gkr491

実験手法

X-RAY DIFFRACTION (2.65 Å)