Book ChapterDOI
Aminoglycoside Antibiotics and Decoding
Joseph D. Puglisi,Scott C. Blanchard,Kam D. Dahlquist,Robert G. Eason,Dominique Fourmy,Stephen R. Lynch,Michael I. Recht,Satoko Yoshizawa +7 more
- pp 419-430
TLDR
This chapter presents an overview of the investigations of how aminoglycoside antibiotics bind to rRNA and the insights these studies have provided into the decoding process and how selectivity for prokaryotes is achieved.Abstract:
Aminoglycoside antibiotics bind directly to 16S rRNA in the 30S subunit of bacterial ribosomes and decrease the fidelity of translation. Aminoglycoside antibiotics remain important therapeutic agents and represent the archetype for RNA-targeted antibiotics. This chapter presents an overview of the investigations of how aminoglycoside antibiotics bind to rRNA and the insights these studies have provided into the decoding process. Throughout the chapter, the term "aminoglycoside" will implicitly refer to this subclass. It is within this conserved decoding region RNA that aminoglycoside antibiotics bind. The chemical groups that are common among aminoglycoside antibiotics direct specific interaction with the RNA. The major sequence difference between all prokaryotic ribosomes and all eukaryotic ribosomes in the aminoglycoside binding site is an A1408-toG1408 change. However, only low-level resistance was observed to G418 and paromomycin, which are the most effective aminoglycosides against eukaryotic organisms. The major mechanism of aminoglycoside resistance is enzymatic modification of the drug. Molecular contacts between A1492 and A1493 and mRNA during decoding may also explain the miscoding induced by aminoglycoside antibiotics. The work on aminoglycoside antibiotics has revealed the details of how aminoglycosides bind to the ribosome, how resistance occurs, and how selectivity for prokaryotes is achieved. Only the combination of structure determination, biochemical, and biophysical approaches provides true insights into the workings of the ribosome. The use of a small oligonucleotide was essential for this work.read more
Citations
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Journal ArticleDOI
Cleavage of the A site mRNA codon during ribosome pausing provides a mechanism for translational quality control.
TL;DR: It is shown that, during the pausing of a bacterial ribosome, the mRNA being translated is cleaved at a site within or immediately adjacent to the A site codon.
Journal ArticleDOI
Coupling of Drug Protonation to the Specific Binding of Aminoglycosides to the A Site of 16 S rRNA: Elucidation of the Number of Drug Amino Groups Involved and their Identities
TL;DR: The results clearly identify drug protonation reactions as important thermodynamic participants in the specific binding of 2-DOS aminoglycoside antibiotics to the A site of 16S rRNA.
Journal ArticleDOI
Aminoglycoside activity observed on single pre-translocation ribosome complexes
TL;DR: Using single-molecule fluorescence resonance energy transfer (smFRET) methods, it is shown that high-affinity aminoglycoside binding to the conserved decoding site region of the functional pre-translocation ribosome complex specifically remodels the nature of intrinsic dynamic processes within the particle.
Journal ArticleDOI
The ribosome-bound chaperones RAC and Ssb1/2p are required for accurate translation in Saccharomyces cerevisiae.
TL;DR: It is concluded that RAC and Ssb1/2p are crucial in maintaining translational fidelity beyond their postulated role as chaperones for nascent polypeptides.
Journal ArticleDOI
SsrA-mediated protein tagging in the presence of miscoding drugs and its physiological role in Escherichia coli.
TL;DR: The aim of the present study was to address how miscoding antibiotics affect the read‐through of stop codons and SsrA‐mediated protein tagging.
References
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Journal ArticleDOI
Crystal Structure of a Group I Ribozyme Domain: Principles of RNA Packing
Jamie H. D. Cate,Anne R. Gooding,Anne R. Gooding,Elaine R. Podell,Elaine R. Podell,Kaihong Zhou,Barbara L. Golden,Barbara L. Golden,Craig E. Kundrot,Thomas R. Cech,Thomas R. Cech,Jennifer A. Doudna +11 more
TL;DR: The structure indicates the extent of RNA packing required for the function of large ribozymes, the spliceosome, and the ribosome.
Journal ArticleDOI
Interaction of antibiotics with functional sites in 16S ribosomal RNA
Danesh Moazed,Harry F. Noller +1 more
TL;DR: Chemical footprinting shows that several classes of antibiotics protect concise sets of highly conserved nucleotides in 16S ribosomal RNA when bound to ribosomes, having strong implications for the mechanism of action of these antibiotics and for the assignment of functions to specific structural features of 16S rRNA.
Journal ArticleDOI
Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes.
TL;DR: A preliminary assessment of the amino acids which may be important in binding aminoglycosides was obtained from data and from the results of mutational analysis of several of the genes encoding am inoglycoside-modifying enzymes.
Journal ArticleDOI
Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.
Toni R. Prezant,J V Agapian,M C Bohlman,Xiangdong Bu,S Oztas,W Q Qiu,K S Arnos,Gino A Cortopassi,Lutfi Jaber,Jerome I. Rotter +9 more
TL;DR: This study offers the first description of a mitochondrial rRNA mutation leading to disease, the first cases of non–syndromic deafness caused by a mitochondrial DNA mutation and the first molecular genetic study of antibiotic–induced ototoxicity.