8SYL

Cryo-EM structure of the Escherichia coli 70S ribosome in complex with amikacin, mRNA, and A-, P-, and E-site tRNAs

This is a non-PDB format compatible entry.

Summary for 8SYL

• Entry DOI: 10.2210/pdb8syl/pdb
• EMDB information: 40882
• Descriptor: 16S Ribosomal RNA, 30S ribosomal protein S10, 30S ribosomal protein S11, ... (60 entities in total)
• Functional Keywords: antibiotic, aminoglycoside, amikacin, cryo-em, trna, ribosome
• Biological source: Escherichia coli; More
• Total number of polymer chains: 56
• Total formula weight: 2232539.56

Authors

Seely, S.M.,Gagnon, M.G. (deposition date: 2023-05-25, release date: 2023-08-09, Last modification date: 2023-11-15)

Primary citation

Seely, S.M.,Parajuli, N.P.,De Tarafder, A.,Ge, X.,Sanyal, S.,Gagnon, M.G.
Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome.
Nat Commun, 14:4666-4666, 2023

PubMed Abstract: Aminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function. Amikacin, the semisynthetic derivative of kanamycin, is commonly used for treating severe infections with multidrug-resistant, aerobic Gram-negative bacteria. Amikacin carries the 4-amino-2-hydroxy butyrate (AHB) moiety at the N amino group of the central 2-deoxystreptamine (2-DOS) ring, which may confer amikacin a unique ribosome inhibition profile. Here we use in vitro fast kinetics combined with X-ray crystallography and cryo-EM to dissect the mechanisms of ribosome inhibition by amikacin and the parent compound, kanamycin. Amikacin interferes with tRNA translocation, release factor-mediated peptidyl-tRNA hydrolysis, and ribosome recycling, traits attributed to the additional interactions amikacin makes with the decoding center. The binding site in the large ribosomal subunit proximal to the 3'-end of tRNA in the peptidyl (P) site lays the groundwork for rational design of amikacin derivatives with improved antibacterial properties.

PubMed: 37537169
DOI: 10.1038/s41467-023-40416-5

Experimental method

ELECTRON MICROSCOPY (2.9 Å)