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Publication Abstract from PubMed

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(1) 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.

Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome.,Seely SM, Parajuli NP, De Tarafder A, Ge X, Sanyal S, Gagnon MG Nat Commun. 2023 Aug 3;14(1):4666. doi: 10.1038/s41467-023-40416-5. PMID:37537169^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.