Evolutionary Conservation of the Copper-Dependent Thiol Oxidase Activity of Selenium-Binding Proteins
Year: 2026
Type: article
Abstract: Human selenium-binding protein 1 (SELENBP1) is a methanethiol oxidase (MTO), converting methanethiol (MT) to hydrogen sulfide (H2S), hydrogen peroxide (H2O2) and formaldehyde (HCHO). SELENBP1 has orthologs in all domains of life. RdMTO, an orthologous enzyme recently identified in the marine bacterium Roseobacter denitrificans, was postulated to require the cysteine residue closest to its C-terminus, Cys448, for MT binding and to oxidize MT to sulfane sulfur (S0) rather than to H2S. SELENBP1 and RdMTO exhibit ~53% sequence identity, with Cys448 (numbered Cys466 in SELENBP1) and amino acids required for copper binding being conserved. Therefore, we here compared the MTO activity of recombinant SELENBP1 and RdMTO. We found that SELENBP1, like RdMTO, converts MT as well as structurally related alkyl thiols to form H2S, H2O2 and, in the case of MT, HCHO in a strictly copper-dependent manner. MTO activity of both proteins was lowered but not abrogated upon mutation of their respective C-terminal cysteine residue. Thus, the catalytic mechanism of selenium-binding proteins that act as copper-dependent MTOs appears to be evolutionarily conserved from bacteria to humans. Presumably, this enzyme is an early evolutionary invention of prokaryotes, in order to cope with toxic thiols in their environment.
Source: Antioxidants
Institution: Friedrich Schiller University Jena
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Award: G853745317
OpenAlex ID: W7212131380