5XF5

Nucleosome core particle with an adduct of a binuclear RAPTA (Ru-arene-phosphaadamantane) compound having a 1,2-diphenylethylenediamine linker (R,S-configuration)

5XF5 の概要

• エントリーDOI: 10.2210/pdb5xf5/pdb
• 関連するPDBエントリー: 5XF3 5XF4 5XF6
• 分子名称: Histone H3.1, SULFATE ION, Histone H4, ... (10 entities in total)
• 機能のキーワード: nucleosome, histone adduct, ruthenium compound, binuclear metal-based agent, structural protein-dna complex, structural protein/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: P68431 P62805 P04908 P06899
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 200674.40

構造登録者

Ma, Z.,Adhireksan, Z.,Murray, B.S.,Dyson, P.J.,Davey, C.A. (登録日: 2017-04-07, 公開日: 2017-10-11, 最終更新日: 2023-11-22)

主引用文献

Davey, G.E.,Adhireksan, Z.,Ma, Z.,Riedel, T.,Sharma, D.,Padavattan, S.,Rhodes, D.,Ludwig, A.,Sandin, S.,Murray, B.S.,Dyson, P.J.,Davey, C.A.
Nucleosome acidic patch-targeting binuclear ruthenium compounds induce aberrant chromatin condensation
Nat Commun, 8:1575-1575, 2017

PubMed Abstract: The 'acidic patch' is a highly electronegative cleft on the histone H2A-H2B dimer in the nucleosome. It is a fundamental motif for protein binding and chromatin dynamics, but the cellular impact of targeting this potentially therapeutic site with exogenous molecules remains unclear. Here, we characterize a family of binuclear ruthenium compounds that selectively target the nucleosome acidic patch, generating intra-nucleosomal H2A-H2B cross-links as well as inter-nucleosomal cross-links. In contrast to cisplatin or the progenitor RAPTA-C anticancer drugs, the binuclear agents neither arrest specific cell cycle phases nor elicit DNA damage response, but rather induce an irreversible, anomalous state of condensed chromatin that ultimately results in apoptosis. In vitro, the compounds induce misfolding of chromatin fibre and block the binding of the regulator of chromatin condensation 1 (RCC1) acidic patch-binding protein. This family of chromatin-modifying molecules has potential for applications in drug development and as tools for chromatin research.

PubMed: 29146919
DOI: 10.1038/s41467-017-01680-4

実験手法

X-RAY DIFFRACTION (2.82 Å)