Selenol (-SeH) as a target for mercury and gold in biological systems: Contributions of mass spectrometry and atomic spectroscopy
Résumé
The selenol (-SeH) group of selenocysteine (SeCys), a cysteine analogue and a more potent nucleophile, has often been considered as a potential target of toxic trace metals and metalloids (Hg, As) and metallodrugs (Au, Pt), privileged with regard to more abundant aminoacids, such as cysteine or histidine. However, the formal evidence of the occurrence of the Se-metal bond, the involvement of selenol and the exact location of the Se-metal bonds in proteins containing several SeCys residues, especially in vivo, have largely been missing. This review discusses critically the contributions of the state-of-the-art analytical mass spectrometric and atomic spectroscopic techniques to studies of metal-binding sites with the different level of confidence in terms of demonstration of the occurrence of the Se-metal binding and the location of the binding site within the Se-containing molecule. They include methods indicating potential interactions on the basis of evidence of co-elution (HPLC-ICP MS) and co-localisation (laser ablation ICP MS, XRF, nanoSIMS) of selenium and the metal(s), methods confirming the evidence of the formation of Se-containing molecule – metal adducts (electrospray and MALDI MS), methods proving the existence of the actual Se-Me bond (EXAFS and XANES) and, finally, methods able to identify the actual binding site in proteins containing several SeCys residues (top-down MS, MS of tryptic digests of metal-protein adducts). The state of the art of in-vitro studies of metal-ion interactions with model SeCys-containing compounds at different levels of molecular complexity (selenoproteins, mimics selenopeptides, selenocysteine) and oxidation (Se-Se, Se-S bridges) as well as that of in-vivo studies are critically reviewed.