ArticlePloS one2018
Discovery of fragments that target key interactions in the signal recognition particle (SRP) as potential leads for a new class of antibiotics.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed.
- Chemical genomics informs antibiotic and essential gene function in Acinetobacter baumannii.PLoS genetics · 2025Article
- Delineation of global, absolutely essential and conditionally essential pangenomes of Porphyromonas gingivalis.Scientific reports · 2024Article
- Article
- Noncanonical Functions and Cellular Dynamics of the Mammalian Signal Recognition Particle Components.Frontiers in molecular biosciences · 2021Review
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Given the increasing incidence of antibiotic resistance, antibiotics that employ new strategies are urgently needed. Bacterial survival is dependent on proper function of the signal recognition particle (SRP) and its receptor (FtsY). A unique set of interactions in FtsY:SRP-RNA represents a promising candidate for new antibiotic development as no antibiotic targets this complex and these interactions are functionally replaced by protein:protein interactions in eukaryotes. We used a Fragment Based Drug Design (FBDD) approach to search for new compounds that can bind FtsY, and have identified three lead fragments. In vitro and in vivo analyses have shown that despite a high micromolar binding affinity, one fragment has some antimicrobial properties. X-ray structures of E. coli FtsY:fragments reveal the fragments bind in the targeted RNA interaction site. Our results show that FBDD is a suitable approach for targeting FtsY:SRP-RNA for antibiotic development and opens the possibility of targeting protein:RNA interactions in general.
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Registered trials
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