Skip to Main content Skip to Navigation
Journal articles

Understanding the role of intermolecular interactions between lissoclimides and the eukaryotic ribosome

Abstract : Natural products that target the eukaryotic ribosome are promising therapeutics to treat a variety of cancers. It is therefore essential to determine their molecular mechanism of action to fully understand their mode of interaction with the target and to inform the development of new synthetic compounds with improved potency and reduced cytotoxicity. Toward this goal, we have previously established a short synthesis pathway that grants access to multiple congeners of the lissoclimide family. Here we present the X-ray co-crystal structure at 3.1 Å resolution of C45, a potent congener with two A-ring chlorine-bearing stereogenic centers with 'unnatural' configurations, with the yeast 80S ribosome, intermolecular interaction energies of the C45/ribosome complex, and single-molecule FRET data quantifying the impact of C45 on both human and yeast ribosomes. Together, these data provide new insights into the role of unusual non-covalent halogen bonding interactions involved in the binding of this synthetic compound to the 80S ribosome.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03659840
Contributor : Gulnara Yusupova Connect in order to contact the contributor
Submitted on : Thursday, May 5, 2022 - 1:38:00 PM
Last modification on : Friday, May 6, 2022 - 11:40:26 AM

Links full text

Identifiers

Collections

Citation

Simone Pellegrino, Mélanie Meyer, Zef Könst, Mikael Holm, Vamsee Voora, et al.. Understanding the role of intermolecular interactions between lissoclimides and the eukaryotic ribosome. Nucleic Acids Research, Oxford University Press, 2019, 47 (6), pp.3223-3232. ⟨10.1093/nar/gkz053⟩. ⟨hal-03659840⟩

Share

Metrics

Record views

13