Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor

Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoli...

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Bibliographic Details
Published in:Environmental science & technology 2011-02, Vol.45 (3), p.937-942
Main Authors: VanEngelen, Michael R, Szilagyi, Robert K, Gerlach, Robin, Lee, Brady D, Apel, William A, Peyton, Brent M
Format: Article
Language:English
Subjects:
BACTERIA
BENZOQUINONES
Biological and medical sciences
CATIONS
Chemical and industrial products toxicology. Toxic occupational diseases
Computer Simulation
CRYSTAL STRUCTURE
Environmental Processes
ENVIRONMENTAL SCIENCES
Eukaryotes
IN VITRO
IN VIVO
Ligands
Mass spectrometry
MASS SPECTROSCOPY
Medical sciences
METABOLISM
Metals and various inorganic compounds
Models, Biological
Models, Chemical
NITROGEN
OXYGEN
PQQ Cofactor - chemistry
Prokaryotes
Proteins
Pseudomonas aeruginosa - drug effects
PYRIDINE
Radioactive Pollutants - chemistry
Radioactive Pollutants - toxicity
SIMULATION
Spectrometry, Mass, Electrospray Ionization
Spectrophotometry, Ultraviolet
SPECTROSCOPY
Spectrum analysis
Studies
TOXICITY
Toxicity Tests, Acute
Toxicology
URANIUM
Uranium - chemistry
Uranium - toxicity
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Summary:Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoline quinone (PQQ)-dependent growth and metabolism by uranyl cations. Electrospray-ionization mass spectroscopy, UV−vis optical spectroscopy, competitive Ca2+/uranyl binding studies, relevant crystal structures, and molecular modeling unequivocally indicate the preferred binding of uranyl simultaneously to the carboxyl oxygen, pyridine nitrogen, and quinone oxygen of the PQQ molecule. The observed toxicity patterns are consistent with the biotic ligand model of acute metal toxicity. In addition to the environmental implications, this work represents the first proposed molecular mechanism of uranium toxicity in bacteria, and has relevance for uranium toxicity in many living systems.
ISSN:0013-936X
1520-5851
DOI:10.1021/es101754x