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Bacterial Ribosome (bacterial + ribosome)

Distribution by Scientific Domains
Life Sciences60%

Selected Abstracts

Conformational Transition in the Aminoacyl t-RNA Site of the Bacterial Ribosome both in the Presence and Absence of an Aminoglycoside Antibiotic

CHEMICAL BIOLOGY & DRUG DESIGN, Issue 5 2007
Samy O. Meroueh
Peptide bonds are made at the ribosomal decoding site. Structural information reveals that two bases in the RNA that constitute the decoding site, A1492 and A1493, can have both intrahelical and extrahelical conformations. Aminoglycoside antibiotics bind to the decoding site, and the structural information reveals the two bases in the extrahelical positions. We have shown by explicit-solvent molecular dynamics simulations and free-energy calculations that ribosomal RNA bases A1492 and A1493 are inherently prone to sampling conformational states that include both intrahelical and extrahelical positions. The simulations reveal that base flipping occurs through the minor groove of the double helix. Furthermore, free-energy calculations for the conformational change of the bases to the extrahelical positions in both processes are exergonic and highly favorable. It is likely that the correct codon-anticodon recognition by mRNA and tRNA arrests the bases in extrahelical conformations in the course of normal translation. In contrast, the sequestration of the aminoglycoside antibiotic at the decoding site facilitates the conformational change of the bases to the extrahelical position. Once the antibiotic is bound, the extrahelical positions for the bases are highly favored based on contributions by both electrostatic and entropic components of the free energy for the process. [source]

Ribosome,DnaK interactions in relation to protein folding

MOLECULAR MICROBIOLOGY, Issue 6 2003
Jaydip Ghosh
Summary Bacterial ribosomes or their 50S subunit can refold many unfolded proteins. The folding activity resides in domain V of 23S RNA of the 50S subunit. Here we show that ribosomes can also refold a denatured chaperone, DnaK, in vitro, and the activity may apply in the folding of nascent DnaK polypeptides in vivo. The chaperone was unusual as the native protein associated with the 50S subunit stably with a 1:1 stoichiometry in vitro. The binding site of the native protein appears to be different from the domain V of 23S RNA, the region with which denatured proteins interact. The DnaK binding influenced the protein folding activity of domain V modestly. Conversely, denatured protein binding to domain V led to dissociation of the native chaperone from the 50S subunit. DnaK thus appears to depend on ribosomes for its own folding, and upon folding, can rebind to ribosome to modulate its general protein folding activity. [source]

Binding of Helix-Threading Peptides to E. coli 16S Ribosomal RNA and Inhibition of the S15,16S Complex

CHEMBIOCHEM, Issue 12 2005
Barry D. Gooch
Abstract Helix-threading peptides (HTPs) constitute a new class of small molecules that bind selectively to duplex RNA structures adjacent to helix defects and project peptide functionality into the dissimilar duplex grooves. To further explore and develop the capabilities of the HTP design for binding RNA selectively, we identified helix 22 of the prokaryotic ribosomal RNA 16S as a target. This helix is a component of the binding site for the ribosomal protein S15. In addition, the S15,16S RNA interaction is important for the ordered assembly of the bacterial ribosome. Here we present the synthesis and characterization of helix-threading peptides that bind selectively to helix 22 of E. coli 16S RNA. These compounds bind helix 22 by threading intercalation placing the N termini in the minor groove and the C termini in the major groove. Binding is dependent on the presence of a highly conserved purine-rich internal loop in the RNA, whereas removal of the loop minimally affects binding of the classical intercalators ethidium bromide and methidiumpropyl,EDTA,Fe (MPE,Fe). Moreover, binding selectivity translates into selective inhibition of formation of the S15,16S complex. [source]

Cover Picture: Targeting RNA with Small Molecules (ChemBioChem 10/2003)

CHEMBIOCHEM, Issue 10 2003
Yitzhak Tor Prof. Dr.
Abstract The cover picture shows the processes involved in the search for small molecules as potent and selective RNA binders. Motivation comes from the desire to control cell function at the RNA level and to identify novel approaches to specifically combat pathogens by targeting their unique RNA sequences or RNA,protein complexes. Inspiration comes from nature; in particular, from aminoglycosides, a family of naturally occurring antibiotics that has been shown to target the bacterial ribosome. The discovery process involves identifying RNA targets (schematically shown as a ribosome or a virus), devising unique assays (e.g. a solid-phase assay), and generating the necessary knowledge and lead structures through design, synthesis, and systematic evaluation of biological activity. Further details can be found in the article by Y. Tor on p. 998 ff. [source]

Properties of Human Mitochondrial Ribosomes

IUBMB LIFE, Issue 9 2003
Thomas W. O'Brien
Abstract Mammalian mitochondrial ribosomes (55S) differ unexpectedly from bacterial (70S) and cytoplasmic ribosomes (80S), as well as other kinds of mitochondrial ribosomes. Typical of mammalian mitochondrial ribosomes, the bovine mitochondrial ribosome has been developed as a model system for the study of human mitochondrial ribosomes, to address several questions related to the structure, function, biosynthesis and evolution of these interesting ribosomes. Bovine mitochondrial ribosomal proteins (MRPs) from each subunit have been identified and characterized with respect to individuality and electrophoretic properties, amino acid sequence, topographic disposition, RNA binding properties, evolutionary relationships and reaction with affinity probes of ribosomal functional domains. Several distinctive properties of these ribosomes are being elucidated, including their antibiotic susceptibility and composition. Human mitochondrial ribosomes lack several of the major RNA stem structures of bacterial ribosomes but they contain a correspondingly higher protein content (as many as 80 proteins), suggesting a model where proteins have replaced RNA structural elements during the evolution of these ribosomes. Despite their lower RNA content they are physically larger than bacterial ribosomes, because of the 'extra' proteins they contain. The extra proteins in mitochondrial ribosomes are 'new' in the sense that they are not homologous to proteins in bacterial or cytoplasmic ribosomes. Some of the new proteins appear to be bifunctional. All of the mammalian MRPs are encoded in nuclear genes (a separate set from those encoding cytoplasmic ribosomal proteins) which are evolving more rapidly than those encoding cytoplasmic ribosomal proteins. The MRPs are imported into mitochondria where they assemble coordinately with mitochondrially transcribed rRNAs into ribosomes that are responsible for translating the 13 mRNAs for essential proteins of the oxidative phosphorylation system. IUBMB Life, 55: 505-513, 2003 [source]