Abstract:
:The selective and potent inhibition of mitochondrial translation in Saccharomyces cerevisiae by pentamidine suggests a novel antimicrobial action for this drug. Electrophoresis mobility shift assay, T1 ribonuclease footprinting, hydroxyl radical footprinting and isothermal titration calorimetry collectively demonstrated that pentamidine non-specifically binds to two distinct classes of sites on tRNA. The binding was driven by favorable entropy changes indicative of a large hydrophobic interaction, suggesting that the aromatic rings of pentamidine are inserted into the stacked base pairs of tRNA helices. Pentamidine binding disrupts the tRNA secondary structure and masks the anticodon loop in the tertiary structure. Consistently, we showed that pentamidine specifically inhibits tRNA aminoacylation but not the cognate amino acid adenylation. Pentamidine inhibited protein translation in vitro with an EC(50) equivalent to that binds to tRNA and inhibits tRNA aminoacylation in vitro, but drastically higher than that inhibits translation in vivo, supporting the established notion that the antimicrobial activity of pentamidine is largely due to its selective accumulation by the pathogen rather than by the host cell. Therefore, interrupting tRNA aminoacylation by the entropy-driven non-specific binding is an important mechanism of pentamidine in inhibiting protein translation, providing new insights into the development of antimicrobial drugs.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Sun T,Zhang Ydoi
10.1093/nar/gkm1180subject
Has Abstractpub_date
2008-03-01 00:00:00pages
1654-64issue
5eissn
0305-1048issn
1362-4962pii
gkm1180journal_volume
36pub_type
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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abstract::SplicePort is a web-based tool for splice-site analysis that allows the user to make splice-site predictions for submitted sequences. In addition, the user can also browse the rich catalog of features that underlies these predictions, and which we have found capable of providing high classification accuracy on human s...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki511
更新日期:2005-04-14 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:
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journal_title:Nucleic acids research
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更新日期:2010-07-01 00:00:00
abstract::A comparison of gene structure, sequence, and transcription pattern of heat shock loci 93D of Drosophila melanogaster and 48B of Drosophila hydei has been performed. Both heat shock loci consist of an unique region that is flanked by an internally repetitive element. Different members of these elements are highly cons...
journal_title:Nucleic acids research
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更新日期:1987-04-24 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:1984-07-11 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2009-06-01 00:00:00
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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abstract::Alternative splicing and polyadenylation were observed pervasively in eukaryotic messenger RNAs. These alternative isoforms could either be consequences of physiological regulation or stochastic noise of RNA processing. To quantify the extent of stochastic noise in splicing and polyadenylation, we analyzed the alterna...
journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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abstract::The development of genetic switches and their integrated forms (genetic circuits) with desired specifications/functions is key for success in synthetic biology. Due to the difficulty in rational design, genetic switches and circuits with desirable specifications are mostly obtained by directed evolution. Based on a vi...
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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journal_title:Nucleic acids research
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更新日期:2018-03-16 00:00:00