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Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome
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- Seely, Savannah M. (författare)
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA
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- Parajuli, Narayan P., 1989- (författare)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
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- De Tarafder, Arindam (författare)
- Uppsala universitet,Molekylärbiologi
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- Ge, Xueliang (författare)
- Uppsala universitet,Molekylärbiologi
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- Sanyal, Suparna (författare)
- Uppsala universitet,Molekylärbiologi
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- Gagnon, Matthieu G. (författare)
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA
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(creator_code:org_t)
- Springer Nature, 2023
- 2023
- Engelska.
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 N1 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.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Strukturbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Structural Biology (hsv//eng)
Nyckelord
- Antibiotics
- aminoglycosides
- amikacin
- kanamycin
- ribosome
- translation
- peptide release
- tRNA translocation
- ribosome recycling.
- Biology with specialization in Molecular Biology
- Biologi med inriktning mot molekylärbiologi
- Biology with specialization in Structural Biology
- Biologi med inriktning mot strukturbiologi
- Biokemi
- Biochemistry
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