8EV6

Crystal structure of the Thermus thermophilus 70S ribosome in complex with amikacin, mRNA, and A-, P-, and E-site tRNAs

This is a non-PDB format compatible entry.

Summary for 8EV6

• Entry DOI: 10.2210/pdb8ev6/pdb
• Descriptor: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (60 entities in total)
• Functional Keywords: amikacin, antibiotic, aminoglycoside, 70s ribosome, inhibitor, trna, ribosome
• Biological source: Escherichia coli; More
• Total number of polymer chains: 112
• Total formula weight: 4563752.26

Authors

Seely, S.M.,Gagnon, M.G. (deposition date: 2022-10-19, 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

X-RAY DIFFRACTION (2.946 Å)