Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au–Se adduct

@article{JacksonRosario2009AuranofinDS,
  title={Auranofin disrupts selenium metabolism in Clostridium difficile by forming a stable Au–Se adduct},
  author={Sarah Jackson-Rosario and Darin M. Cowart and Andrew Myers and Rebecca J. Tarrien and Rodney L. Levine and Robert A. Scott and William T. Self},
  journal={JBIC Journal of Biological Inorganic Chemistry},
  year={2009},
  volume={14},
  pages={507-519}
}
Clostridium difficile is a nosocomial pathogen whose incidence and importance are on the rise. Previous work in our laboratory characterized the central role of selenoenzyme-dependent Stickland reactions in C. difficile metabolism. In this work we have identified, using mass spectrometry, a stable complex formed upon reaction of auranofin (a gold-containing drug) with selenide in vitro. X-ray absorption spectroscopy supports the structure that we proposed on the basis of mass-spectrometric data… Expand
A Selenium-Dependent Xanthine Dehydrogenase Triggers Biofilm Proliferation in Enterococcus faecalis through Oxidant Production
TLDR
Evidence is provided that an SDMH is involved in biofilm formation in Enterococcus faecalis, contributing to oxidant production either directly or alternatively through its involvement in redox-dependent processes linked to oxidants production. Expand
Direct Observation of Methylmercury and Auranofin Binding to Selenocysteine in Thioredoxin Reductase.
TLDR
The results demonstrate for the first time the direct and complete binding of the metal atom of the inhibitors to the selenium atom in TrxR1 for both methylmercury and auranofin, indicating that TrXR1 inhibition indeed can be attributed to such direct metal-selenium binding. Expand
Targeting selenium metabolism and selenoproteins: novel avenues for drug discovery.
TLDR
This review summarizes the recent finding on these two avenues for drug discovery, and puts this work in context with the larger field of selenium biology. Expand
Selenoproteins in Archaea and Gram-positive bacteria.
TLDR
This review summarizes current knowledge about the metabolic pathways of Archaea and Gram-positive bacteria where selenium is involved, about the known selenoproteins, and about the respective pathways employed in selenocsteine synthesis. Expand
Exposure to Silver Nanoparticles Inhibits Selenoprotein Synthesis and the Activity of Thioredoxin Reductase
TLDR
Exposure to AgNPs leads to the inhibition of selenoprotein synthesis and inhibition of TrxR1, and it is proposed these two sites of action comprise the likely mechanism underlying increases in oxidative stress, increases endoplasmic reticulum stress, and reduced cell proliferation during exposure to Ag. Expand
Selenoenzymes and Selenium Trafficking: An Emerging Target for Therapeutics
TLDR
Emerging evidence suggests that many well-known cancer drugs target a specific class of selenoproteins in mammals, lending credence to the notion that selenocsteine-based proteins may indeed already be substantial drug targets in the clinic. Expand
Proline-Dependent Regulation of Clostridium difficile Stickland Metabolism
TLDR
The identification of PrdR is reported, a protein that activates transcription of the PR-encoding genes in the presence of proline and negatively regulates the GR-encoded genes, suggesting that PrdC is a central metabolism regulator that controls preferential utilization of prolines and glycine to produce energy via the Stickland reactions. Expand
Selenium Metabolism in Prokaryotes
Biologically active selenium occurs as a modification in tRNA, noncovalently attached cofactor, or as the amino acid selenocysteine, exerting functions key to the metabolism of the organism harboringExpand
Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria
TLDR
It is demonstrated that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro, which affects the biodiversity of gut microbiota and faecal metabolite profiles. Expand
Repurposing auranofin as a Clostridioides difficile therapeutic.
TLDR
Auranofin significantly reduces sporulation and toxin production under in vitro conditions and in infected mice in vivo, and shows promise as a prospective therapeutic option for C. difficile infections. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 98 REFERENCES
Analysis of Proline Reduction in the Nosocomial Pathogen Clostridium difficile
TLDR
Results show that Stickland reactions are key to the growth of C. difficile and that the mechanism of PR may differ significantly from that of previously studied PR from nonpathogenic species. Expand
Selenoprotein synthesis in E. coli. Purification and characterisation of the enzyme catalysing selenium activation.
TLDR
Speculation that the product of SELD is a phosphoselenoate with the phosphate moiety derived phosphoseLenoate from the gamma-phosphate group of ATP is supported by the finding that neither adenosine 5'-[alpha,beta-methylene]triph phosphate nor adenosines 5'-,[beta,gamma-methylenes]triPhosphate served as substrates in the reaction. Expand
From selenium to selenoproteins: synthesis, identity, and their role in human health.
TLDR
The function of most selenoproteins is currently unknown; however, thioredoxin reductases, glutathione peroxidases and thyroid hormone deiodinases are well characterised selenobroteins involved in redox regulation of intracellular signalling, redox homeostasis and thyroid hormones metabolism. Expand
Coordination of selenium to molybdenum in formate dehydrogenase H from Escherichia coli.
TLDR
It is shown that addition of formate to the native enzyme induces a signal typical of Mo(V) species, and it is concluded that it is the Se atom of the SeCys-140 residue in the protein that is coordinated directly with Mo. Expand
Monoselenophosphate: synthesis, characterization, and identity with the prokaryotic biological selenium donor, compound SePX.
TLDR
Addition of chemically prepared monoselenophosphate caused a dose-dependent decrease in the amount of 75Se incorporated into tRNAs from 75SePX generated in situ by SELD enzyme. Expand
Thioredoxin reductase as a pathophysiological factor and drug target.
TLDR
The hypothesis that TrxR and extracellular thioredoxin play a pathophysiologic role in chronic diseases such as rheumatoid arthritis, Sjögren's syndrom, AIDS, and certain malignancies, is substantiated by biochemical, virological, and clinical evidence. Expand
Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein
TLDR
It is established that Trypanosoma, Leishmania and likely other Kinetoplastida utilize and depend on the trace element selenium, and this dependence is due to occurrence of selenum in at least three selenoproteins. Expand
Selenium-dependent growth of Treponema denticola: evidence for a clostridial-type glycine reductase
TLDR
Findings strongly support the notion that T. denticola ferments amino acids via the activity of glycine reductase, an enzyme previously thought to be restricted to gram-positive bacteria. Expand
[40] Selenium-dependent clostridial glycine reductase
Publisher Summary This chapter talks about selenium-dependent clostridial glycine reductase enzyme. The reductive deamination of glycine to acetate and ammonia serves as a terminal electron acceptorExpand
The Plasmodium selenoproteome
TLDR
Dependence of the plasmodial parasites on selenium suggests possible strategies for antimalarial drug development and conservation of Sec insertion between Apicomplexa and animals is suggested. Expand
...
1
2
3
4
5
...