Molecular Mimicry in Mercury Toxicology

Molecular mimicry occurs when one molecular entity is “mistaken” for another by cellular or other biological processes, and is thought to arise from structural similarities between the two molecules in question. It has been postulated by others to be important in the mechanism of uptake of toxic metal species into living tissues. A widely accepted example is the transport of methylmercury−cysteine species, which are thought to mimic the amino acid methionine. We have used mass spectrometry and mercury LIII-edge X-ray absorption spectroscopy to understand the solution structure of complexes between methylmercury and cysteine. With a view to understanding the basis of the suggested molecular mimicry mechanisms, we have used computational chemistry to compare the structure of methionine with that of the dominant solution species l-cysteinato(methyl)mercury(II), and the structure of cystine with that of mercury(II) bis-l-cysteineate. We conclude that the structural similarities between metal compounds and natural products are insufficient to support a mechanism based on molecular mimicry, but instead, mechanisms involving a less-specific mimicry based on similarity with the Lα region of the amino acid part of the molecule.