Small Molecule Inhibitors Targeting the Interaction of Ricin Toxin A Subunit with Ribosomes.

ABSTRACT: Ricin toxin A subunit (RTA) removes an adenine from the universally conserved sarcin/ricin loop (SRL) on eukaryotic ribosomes, thereby inhibiting protein synthesis. No high affinity and selective small molecule therapeutic antidotes have been reported against ricin toxicity. RTA binds to the ribosomal P stalk to access the SRL. The interaction anchors RTA to the P protein C-termini at a well-defined hydrophobic pocket, which is on the opposite face relative to the active site. The RTA ribosome binding site has not been previously targeted by small molecule inhibitors. We used fragment screening with surface plasmon resonance to identify small molecular weight lead compounds that bind RTA and defined their interactions by crystallography. We identified five fragments, which bound RTA with m

SUBMITTER: Li XP 

PROVIDER: S-EPMC7678679 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature