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Crosslinking Allosteric Sites on the Nucleosome.
Journal article

Crosslinking Allosteric Sites on the Nucleosome.

  • Batchelor LK Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • De Falco L School of Biological Sciences & NTU Institute of Structural Biology, Nanyang Technological University (NTU), Singapore, Singapore.
  • von Erlach T Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Sharma D School of Biological Sciences & NTU Institute of Structural Biology, Nanyang Technological University (NTU), Singapore, Singapore.
  • Adhireksan Z School of Biological Sciences & NTU Institute of Structural Biology, Nanyang Technological University (NTU), Singapore, Singapore.
  • Roethlisberger U Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
  • Davey CA School of Biological Sciences & NTU Institute of Structural Biology, Nanyang Technological University (NTU), Singapore, Singapore.
  • Dyson PJ Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
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  • 2019-09-04
Published in:
  • Angewandte Chemie (International ed. in English). - 2019
allostery
bioinorganic chemistry
macromolecular crystallography
molecular dynamics simulations
nucleosome structure
Allosteric Site
Cross-Linking Reagents
Models, Molecular
Molecular Structure
Nucleosomes
English Targeting defined histone protein sites in chromatin is an emerging therapeutic approach that can potentially be enhanced by allosteric effects within the nucleosome. Here we characterized a novel hetero-bimetallic compound with a design based on a nucleosomal allostery effect observed earlier for two unrelated drugs-the RuII antimetastasis/antitumor RAPTA-T and the AuI anti-arthritic auranofin. The RuII moiety binds specifically to two H2A glutamate residues on the nucleosome acidic patch, allosterically triggering a cascade of structural changes that promote binding of the AuI moiety to selective histidine residues on H3, resulting in cross-linking sites that are over 35 Å distant. By tethering the H2A-H2B dimers to the H3-H4 tetramer, the hetero-bimetallic compound significantly increases stability of the nucleosome, illustrating its utility as a site-selective cross-linking agent.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/214607
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