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  • Blasticidin S inhibits translation by trapping deformed tRNA on the ribosome.

Blasticidin S inhibits translation by trapping deformed tRNA on the ribosome.

Proceedings of the National Academy of Sciences of the United States of America (2013-07-05)
Egor Svidritskiy, Clarence Ling, Dmitri N Ermolenko, Andrei A Korostelev
ABSTRACT

The antibiotic blasticidin S (BlaS) is a potent inhibitor of protein synthesis in bacteria and eukaryotes. We have determined a 3.4-Å crystal structure of BlaS bound to a 70S⋅tRNA ribosome complex and performed biochemical and single-molecule FRET experiments to determine the mechanism of action of the antibiotic. We find that BlaS enhances tRNA binding to the P site of the large ribosomal subunit and slows down spontaneous intersubunit rotation in pretranslocation ribosomes. However, the antibiotic has negligible effect on elongation factor G catalyzed translocation of tRNA and mRNA. The crystal structure of the antibiotic-ribosome complex reveals that BlaS impedes protein synthesis through a unique mechanism by bending the 3' terminus of the P-site tRNA toward the A site of the large ribosomal subunit. Biochemical experiments demonstrate that stabilization of the deformed conformation of the P-site tRNA by BlaS strongly inhibits peptidyl-tRNA hydrolysis by release factors and, to a lesser extent, peptide bond formation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Blasticidine S hydrochloride
Sigma-Aldrich
Blasticidin S Ready Made Solution, 10 mg/mL (20 mM HEPES), 0.22 μm filtered