Redox active motifs in selenoproteins

Area of Science:

• Biochemistry
• Structural Biology
• Chemical Biology

Background:

• Selenoproteins utilize selenocysteine (Sec), a rare amino acid, as a primary defense against oxidants implicated in aging and diseases.
• Many selenoproteins function as oxidoreductases, featuring Sec-Cys redox motifs critical for their reactivity.

Purpose of the Study:

• To investigate the fundamental properties, conformational preferences, and mobility of Sec-containing redox motifs.
• To determine how selenium incorporation and ring strain influence the reactivity and redox potentials of these motifs.

Main Methods:

• Utilized (77)Se NMR spectroscopy to probe the environment and properties of Sec.
• Employed theoretical calculations to analyze conformational preferences and mobility.
• Measured redox potentials of Sec-containing motifs and their cysteine-only counterparts.

Main Results:

• Observed multiple ring conformations in the oxidized state of Sec motifs, likely stabilized by Se-amide carbon interactions.
• Found that redox potentials of C-terminal motifs increased by 20-25 mV upon conversion from selenenylsulfide to disulfide bonds.
• Demonstrated that changes in ring size or flanking residues also induced similar magnitude shifts in redox potentials.

Conclusions:

• The presence of Sec does not inherently confer unusually low redox potentials to selenoproteins.
• The distinct roles and reactivities of selenoproteins in human health may not solely be attributed to lower redox potentials.