Difference between revisions of "PMID:16356850"

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'''Sudarsan, N , Cohen-Chalamish, S , Nakamura, S , Emilsson, GM  and Breaker, RR '''  (2005) Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine. ''Chem. Biol.'' '''12''':1325-35
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!align=left  |Abstract
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Thiamine metabolism genes are regulated in numerous bacteria by a riboswitch class that binds the coenzyme thiamine pyrophosphate (TPP). We demonstrate that the antimicrobial action of the thiamine analog pyrithiamine (PT) is mediated by interaction with TPP riboswitches in bacteria and fungi. For example, pyrithiamine pyrophosphate (PTPP) binds the TPP riboswitch controlling the tenA operon in Bacillus subtilis. Expression of a TPP riboswitch-regulated reporter gene is reduced in transgenic B. subtilis or Escherichia coli when grown in the presence of thiamine or PT, while mutant riboswitches in these organisms are unresponsive to these ligands. Bacteria selected for PT resistance bear specific mutations that disrupt ligand binding to TPP riboswitches and derepress certain TPP metabolic genes. Our findings demonstrate that riboswitches can serve as antimicrobial drug targets and expand our understanding of thiamine metabolism in bacteria.
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[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16356850 PubMed]
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Online version:[http://dx.doi.org/10.1016/j.chembiol.2005.10.007 10.1016/j.chembiol.2005.10.007]
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Anti-Infective Agents/pharmacology; Bacillus/genetics; Models, Biological; Molecular Structure; Nucleic Acid Conformation; Protein Structure, Tertiary; Pyrithiamine/pharmacology; RNA, Bacterial/drug effects; Thiamine/chemistry; Thiamine/metabolism; Thiamine/pharmacology; Thiamine Pyrophosphate/biosynthesis; Thiamine Pyrophosphate/genetics; Thiamine Pyrophosphate/metabolism
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==Main Points of the Paper ==
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== Materials and Methods Used ==
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==Phenotype Annotations==
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==Notes==
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==References==
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[[Category:Publication]]

Latest revision as of 08:49, 13 October 2012

Citation

Sudarsan, N , Cohen-Chalamish, S , Nakamura, S , Emilsson, GM and Breaker, RR (2005) Thiamine pyrophosphate riboswitches are targets for the antimicrobial compound pyrithiamine. Chem. Biol. 12:1325-35

Abstract

Thiamine metabolism genes are regulated in numerous bacteria by a riboswitch class that binds the coenzyme thiamine pyrophosphate (TPP). We demonstrate that the antimicrobial action of the thiamine analog pyrithiamine (PT) is mediated by interaction with TPP riboswitches in bacteria and fungi. For example, pyrithiamine pyrophosphate (PTPP) binds the TPP riboswitch controlling the tenA operon in Bacillus subtilis. Expression of a TPP riboswitch-regulated reporter gene is reduced in transgenic B. subtilis or Escherichia coli when grown in the presence of thiamine or PT, while mutant riboswitches in these organisms are unresponsive to these ligands. Bacteria selected for PT resistance bear specific mutations that disrupt ligand binding to TPP riboswitches and derepress certain TPP metabolic genes. Our findings demonstrate that riboswitches can serve as antimicrobial drug targets and expand our understanding of thiamine metabolism in bacteria.

Links

PubMed Online version:10.1016/j.chembiol.2005.10.007

Keywords

Anti-Infective Agents/pharmacology; Bacillus/genetics; Models, Biological; Molecular Structure; Nucleic Acid Conformation; Protein Structure, Tertiary; Pyrithiamine/pharmacology; RNA, Bacterial/drug effects; Thiamine/chemistry; Thiamine/metabolism; Thiamine/pharmacology; Thiamine Pyrophosphate/biosynthesis; Thiamine Pyrophosphate/genetics; Thiamine Pyrophosphate/metabolism

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Main Points of the Paper

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Materials and Methods Used

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Phenotype Annotations

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Phenotype of Taxon Information Genotype Information (if known) Condition Information OMP ID OMP Term Name ECO ID ECO Term Name Notes Status
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Notes

References

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