5XF4

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

Summary for 5XF4

• Entry DOI: 10.2210/pdb5xf4/pdb
• Related: 5XF3 5XF5 5XF6
• Descriptor: Histone H3.1, SULFATE ION, Histone H4, ... (10 entities in total)
• Functional Keywords: nucleosome, histone adduct, ruthenium compound, binuclear metal-based agent, structural protein-dna complex, structural protein/dna
• Biological source: Homo sapiens (Human); More
• Cellular location: Nucleus: P68431 P62805 P04908 P06899
• Total number of polymer chains: 10
• Total formula weight: 200674.40

Authors

Ma, Z.,Adhireksan, Z.,Murray, B.S.,Dyson, P.J.,Davey, C.A. (deposition date: 2017-04-07, release date: 2017-10-11, Last modification date: 2023-11-22)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.87 Å)