Related Experiment Video
Updated: Jul 19, 2025
11:19
Isolation of Translating Ribosomes Containing Peptidyl-tRNAs for Functional and Structural Analyses
Published on: February 25, 2011
19.9K
Structural conservation of antibiotic interaction with ribosomes
Helge Paternoga1, Caillan Crowe-McAuliffe1, Lars V Bock2
1Institute for Biochemistry and Molecular Biology, University of Hamburg, Hamburg, Germany.
Nature Structural & Molecular Biology
|August 7, 2023
Summary
High-resolution structures reveal how antibiotics bind to bacterial ribosomes, including the role of water molecules. This insight aids in developing new antimicrobial drugs to combat antibiotic resistance.
Area of Science:
- Structural Biology
- Microbiology
- Drug Discovery
Background:
- Antibiotic resistance is a growing threat, rendering current antimicrobial drugs ineffective.
- The bacterial ribosome is a key target for many antibiotics.
- Understanding precise antibiotic-ribosome interactions is crucial for developing new therapies.
Purpose of the Study:
- To elucidate the detailed structural mechanisms of antibiotic binding to the bacterial ribosome.
- To investigate the role of solvent networks and water molecules in these interactions.
- To provide insights for the development of novel antimicrobial agents.
Main Methods:
- Cryo-electron microscopy (cryo-EM) was used to determine structures.
- 17 distinct antibiotic compounds from six classes were analyzed.
- Structures were resolved at high resolution (1.6–2.2 Å).
Main Results:
- Precise descriptions of antibiotic-ribosome interactions were achieved.
- Ordered water molecules were visualized within antibiotic binding sites, playing a key role.
- Structural conservation in binding modes was observed for antibiotics with similar scaffolds.
- Water molecules are pre-ordered, become ordered upon drug binding, and are displaced by the drug.
Conclusions:
- Detailed structural insights into antibiotic-ribosome interactions, including water networks, are provided.
- Understanding these interactions can guide the design of new antibiotics.
- This research supports the development of novel RNA-targeting therapies.
Related Concept Videos
01:23Types of RNA
64.0K
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
64.0K
01:27Combined Effects of Drugs: Synergism
4.0K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
4.0K
01:29Coordination of Gene Expression Processes in Bacteria
40
The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
40
01:30Development of Antibiotic Resistance
40
Antibiotic resistance is a major public health concern that arises when bacteria evolve mechanisms to withstand the effects of antibiotic treatments. This resistance can be intrinsic, acquired through genetic mutations, or transferred between bacteria via horizontal gene transfer. The development of antibiotic resistance poses significant challenges in treating bacterial infections and necessitates ongoing research to develop new therapeutic strategies.Intrinsic resistance occurs when bacterial...
40
01:44Termination of Translation
25.5K
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is the site where the peptide bond is formed - and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through...
25.5K
01:29Translational Regulation
45
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
45