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

SUBMITTER: Pellegrino S 

PROVIDER: S-EPMC6451132 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature