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Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome
by
Seely, Savannah M.
, Parajuli, Narayan P.
, De Tarafder, Arindam
, Sanyal, Suparna
, Ge, Xueliang
, Gagnon, Matthieu G.
in
101/28
/ 631/337/574/1789
/ 631/45/500
/ 631/535/1266
/ 631/57/2272/1590
/ 631/92/613
/ Amikacin
/ Amikacin - chemistry
/ Amikacin - metabolism
/ Amikacin - pharmacology
/ Aminoglycosides
/ Anti-Bacterial Agents - chemistry
/ Antibiotic resistance
/ Antibiotics
/ Bacteria
/ BASIC BIOLOGICAL SCIENCES
/ Binding sites
/ Biochemistry
/ Biokemi
/ Biologi med inriktning mot molekylärbiologi
/ Biologi med inriktning mot strukturbiologi
/ Biology with specialization in Molecular Biology
/ Biology with specialization in Structural Biology
/ Crystallography
/ Gram-negative bacteria
/ Humanities and Social Sciences
/ Kanamycin
/ Kanamycin - analysis
/ Kanamycin - metabolism
/ Kanamycin - pharmacology
/ Kinetics
/ Models, Molecular
/ multidisciplinary
/ Multidrug resistance
/ peptide release
/ Ribosome
/ ribosome recycling
/ Ribosomes - metabolism
/ RNA
/ RNA, Transfer - metabolism
/ rRNA
/ Science
/ Science & Technology
/ Science (multidisciplinary)
/ Small molecules
/ Transfer RNA
/ translation
/ Translocation
/ tRNA
/ tRNA translocation
/ X-ray crystallography
2023
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Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome
by
Seely, Savannah M.
, Parajuli, Narayan P.
, De Tarafder, Arindam
, Sanyal, Suparna
, Ge, Xueliang
, Gagnon, Matthieu G.
in
101/28
/ 631/337/574/1789
/ 631/45/500
/ 631/535/1266
/ 631/57/2272/1590
/ 631/92/613
/ Amikacin
/ Amikacin - chemistry
/ Amikacin - metabolism
/ Amikacin - pharmacology
/ Aminoglycosides
/ Anti-Bacterial Agents - chemistry
/ Antibiotic resistance
/ Antibiotics
/ Bacteria
/ BASIC BIOLOGICAL SCIENCES
/ Binding sites
/ Biochemistry
/ Biokemi
/ Biologi med inriktning mot molekylärbiologi
/ Biologi med inriktning mot strukturbiologi
/ Biology with specialization in Molecular Biology
/ Biology with specialization in Structural Biology
/ Crystallography
/ Gram-negative bacteria
/ Humanities and Social Sciences
/ Kanamycin
/ Kanamycin - analysis
/ Kanamycin - metabolism
/ Kanamycin - pharmacology
/ Kinetics
/ Models, Molecular
/ multidisciplinary
/ Multidrug resistance
/ peptide release
/ Ribosome
/ ribosome recycling
/ Ribosomes - metabolism
/ RNA
/ RNA, Transfer - metabolism
/ rRNA
/ Science
/ Science & Technology
/ Science (multidisciplinary)
/ Small molecules
/ Transfer RNA
/ translation
/ Translocation
/ tRNA
/ tRNA translocation
/ X-ray crystallography
2023
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Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome
by
Seely, Savannah M.
, Parajuli, Narayan P.
, De Tarafder, Arindam
, Sanyal, Suparna
, Ge, Xueliang
, Gagnon, Matthieu G.
in
101/28
/ 631/337/574/1789
/ 631/45/500
/ 631/535/1266
/ 631/57/2272/1590
/ 631/92/613
/ Amikacin
/ Amikacin - chemistry
/ Amikacin - metabolism
/ Amikacin - pharmacology
/ Aminoglycosides
/ Anti-Bacterial Agents - chemistry
/ Antibiotic resistance
/ Antibiotics
/ Bacteria
/ BASIC BIOLOGICAL SCIENCES
/ Binding sites
/ Biochemistry
/ Biokemi
/ Biologi med inriktning mot molekylärbiologi
/ Biologi med inriktning mot strukturbiologi
/ Biology with specialization in Molecular Biology
/ Biology with specialization in Structural Biology
/ Crystallography
/ Gram-negative bacteria
/ Humanities and Social Sciences
/ Kanamycin
/ Kanamycin - analysis
/ Kanamycin - metabolism
/ Kanamycin - pharmacology
/ Kinetics
/ Models, Molecular
/ multidisciplinary
/ Multidrug resistance
/ peptide release
/ Ribosome
/ ribosome recycling
/ Ribosomes - metabolism
/ RNA
/ RNA, Transfer - metabolism
/ rRNA
/ Science
/ Science & Technology
/ Science (multidisciplinary)
/ Small molecules
/ Transfer RNA
/ translation
/ Translocation
/ tRNA
/ tRNA translocation
/ X-ray crystallography
2023
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Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome
Journal Article
Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome
2023
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Overview
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.
Here the authors use fast kinetics, X-ray crystallography, and cryo-EM to uncover the mechanism of ribosome inhibition by amikacin and kanamycin. They find that amikacin binds near the P-site tRNA, offering new strategies to fight antibiotic resistance.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ Amikacin
/ Anti-Bacterial Agents - chemistry
/ Bacteria
/ Biokemi
/ Biologi med inriktning mot molekylärbiologi
/ Biologi med inriktning mot strukturbiologi
/ Biology with specialization in Molecular Biology
/ Biology with specialization in Structural Biology
/ Humanities and Social Sciences
/ Kinetics
/ Ribosome
/ RNA
/ rRNA
/ Science
/ tRNA
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