Mercury binding to proteins disclosed by ESI MS experiments: The case of three organomercurials.

Autor: Geri A; Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019, Sesto Fiorentino, Florence, Italy., Zineddu S; Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019, Sesto Fiorentino, Florence, Italy., Massai L; Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019, Sesto Fiorentino, Florence, Italy. Electronic address: lara.massai@unifi.it., Ronga L; Université de Pau et des Pays de l'Adour, E2S UPPA, CNRS, IPREM, Pau, France., Lobinski R; Université de Pau et des Pays de l'Adour, E2S UPPA, CNRS, IPREM, Pau, France; Chair of Analytical Chemistry, Warsaw University of Technology, ul.Noakowskiego 3, 00-664 Warszawa, Poland., Gailer J; Department of Chemistry, University of Calgary, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada., Messori L; Laboratory of Metals in Medicine, Department of Chemistry, University of Florence, via della Lastruccia 3, 50019, Sesto Fiorentino, Florence, Italy. Electronic address: luigi.messori@unifi.it.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2024 Mar; Vol. 252, pp. 112479. Date of Electronic Publication: 2024 Jan 06.
DOI: 10.1016/j.jinorgbio.2024.112479
Abstrakt: Solution interactions of three organomercury compounds, i.e., methylmercury chloride, thimerosal and phenylmercury acetate, with a group of biochemically relevant proteins, namely cytochrome c (Cyt c), ribonuclease A (RNase A), carbonic anhydrase I (hCA I), superoxide dismutase (SOD), and serum albumin (HSA), were investigated using an established ESI MS approach. Temporal analysis of sample aliquots provided insight into the binding kinetics, while comparative analysis of the obtained mass spectra disclosed adduct formation of each mercurial with the tested proteins and the relative abundance of the species. The three organomercurials bind, exclusively and tightly, to free cysteine residues as no binding was observed in the case of proteins lacking such groups. hCA I, SOD and HSA formed distinct mercury adducts, preserving the Hg bound alkyl/aryl ligands; yet, the three organomercurials displayed significant differences in reactivity in relation to their chemical structure. The investigation was then extended to analyze the reactions with the C-terminal dodecapeptide of the enzyme human thioredoxin reductase, which contains a characteristic selenol-thiol moiety: tight Hg binding was observed. Notably, this peptide was able to remove effectively and completely the alkyl/aryl ligands of the three tested organomercurials; this behavior may be relevant to the detoxification mechanism of organomercurials in mammals. Finally, a competition experiment was carried out to establish whether protein bound mercury centers may be displaced by other competing metals. Interestingly, and quite unexpectedly, we observed that a protein bound mercury fragment may be partially displaced from its coordination site in hCA I by the medicinal gold compound auranofin.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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