3REK

2.6 Angstrom Crystal Structure of the Nucleosome Core Particle Assembled with a 146 bp Alpha-Satellite DNA (NCP146b) Derivatized with Oxaliplatin

Summary for 3REK

• Entry DOI: 10.2210/pdb3rek/pdb
• Related: 1KX3 1KX4 1KX5 2NZD 3REH 3REI 3REJ 3REL
• Descriptor: Histone H3.2, Histone H4, Histone H2A type1, ... (8 entities in total)
• Functional Keywords: nucleosome, structural protein-dna complex, structural protein/dna
• Biological source: Xenopus laevis (clawed frog,common platanna,platanna); More
• Cellular location: Nucleus: P84233 P62799 P06897 P02281
• Total number of polymer chains: 10
• Total formula weight: 206451.17

Authors

Wu, B.,Davey, C.A. (deposition date: 2011-04-04, release date: 2012-03-14, Last modification date: 2023-09-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.6 Å)