Search: onr:"swepub:oai:DiVA.org:uu-486746" >
Molecular basis of ...
Molecular basis of the pleiotropic effects by the antibiotic amikacin on the ribosome
-
- Seely, Savannah M. (author)
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA
-
- Parajuli, Narayan P., 1989- (author)
- Uppsala universitet,Institutionen för cell- och molekylärbiologi
-
- De Tarafder, Arindam (author)
- Uppsala universitet,Molekylärbiologi
-
show more...
-
- Ge, Xueliang (author)
- Uppsala universitet,Molekylärbiologi
-
- Sanyal, Suparna (author)
- Uppsala universitet,Molekylärbiologi
-
- Gagnon, Matthieu G. (author)
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA
-
show less...
-
(creator_code:org_t)
- Springer Nature, 2023
- 2023
- English.
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
- Related links:
-
https://doi.org/10.1...
-
show more...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- 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)
Keyword
- 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
Publication and Content Type
- vet (subject category)
- art (subject category)
Find in a library
To the university's database