Uranium exerts acute toxicity by binding to pyrroloquinoline quinone cofactor

Environ Sci Technol. 2011 Feb 1;45(3):937-42. doi: 10.1021/es101754x. Epub 2010 Dec 17.

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 Ca(2+)/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computer Simulation
  • Ligands
  • Models, Biological
  • Models, Chemical
  • PQQ Cofactor / chemistry*
  • Pseudomonas aeruginosa / drug effects
  • Radioactive Pollutants / chemistry
  • Radioactive Pollutants / toxicity*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrophotometry, Ultraviolet
  • Toxicity Tests, Acute
  • Uranium / chemistry
  • Uranium / toxicity*

Substances

  • Ligands
  • Radioactive Pollutants
  • Uranium
  • PQQ Cofactor