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Title: Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor

Abstract

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.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Idaho National Lab. (INL), Idaho Falls, ID (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1016203
Report Number(s):
INL/JOU-11-22412
Journal ID: ISSN 0013--936X; TRN: US201112%%259
DOE Contract Number:  
DE-AC07-05ID14517
Resource Type:
Journal Article
Journal Name:
Environmental Science and Technology
Additional Journal Information:
Journal Volume: 45; Journal Issue: 3; Journal ID: ISSN 0013--936X
Country of Publication:
United States
Language:
English
Subject:
54 ENVIRONMENTAL SCIENCES; BACTERIA; BENZOQUINONES; CATIONS; CRYSTAL STRUCTURE; IN VITRO; IN VIVO; MASS SPECTROSCOPY; METABOLISM; NITROGEN; OXYGEN; PYRIDINE; SIMULATION; SPECTROSCOPY; TOXICITY; URANIUM

Citation Formats

VanEngelen, Michael R, Szilagyi, Robert I, Gerlach, Robin, Lee, Brady E, Apel, William A, and Peyton, Brent M. Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor. United States: N. p., 2011. Web. doi:10.1021/es101754x.
VanEngelen, Michael R, Szilagyi, Robert I, Gerlach, Robin, Lee, Brady E, Apel, William A, & Peyton, Brent M. Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor. United States. https://doi.org/10.1021/es101754x
VanEngelen, Michael R, Szilagyi, Robert I, Gerlach, Robin, Lee, Brady E, Apel, William A, and Peyton, Brent M. 2011. "Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor". United States. https://doi.org/10.1021/es101754x.
@article{osti_1016203,
title = {Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor},
author = {VanEngelen, Michael R and Szilagyi, Robert I and Gerlach, Robin and Lee, Brady E and Apel, William A and Peyton, Brent M},
abstractNote = {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.},
doi = {10.1021/es101754x},
url = {https://www.osti.gov/biblio/1016203}, journal = {Environmental Science and Technology},
issn = {0013--936X},
number = 3,
volume = 45,
place = {United States},
year = {Tue Feb 01 00:00:00 EST 2011},
month = {Tue Feb 01 00:00:00 EST 2011}
}