UMass Chan Medical School Faculty Publications


Blasticidin S inhibits translation by trapping deformed tRNA on the ribosome

UMMS Affiliation

RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Crystallography, X-Ray; Fluorescence Resonance Energy Transfer; Models, Molecular; Nucleosides; Protein Biosynthesis; RNA, Transfer; Ribosomes; Thermus thermophilus


Biochemistry | Molecular Biology


The antibiotic blasticidin S (BlaS) is a potent inhibitor of protein synthesis in bacteria and eukaryotes. We have determined a 3.4-A crystal structure of BlaS bound to a 70StRNA 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.

DOI of Published Version



Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12283-8. doi: 10.1073/pnas.1304922110. Epub 2013 Jul 3. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID