Selenocysteine

Abstract The trace element selenium is present in the form of selenocysteine in selected proteins of organisms from all three domains of life. Most of the selenoproteins (i.e. proteins containing selenocysteine) investigated thus far are oxidoreductases with selenocysteine present in the active site and playing a crucial role in – or creating the required environment for – catalysis. Selenocysteine incorporation is DNA encoded, determined by the UGA codon, and occurs via a unique mechanism representing an expansion of the genetic code. Despite the conceptual conservation of the principal mechanism of selenocysteine synthesis and incorporation in all lines of descent, the bacterial system differs from the archaeal/eukaryal system. Detailed biochemical and structural knowledge of selenoprotein synthesis has allowed rewiring bacterial translation for targeted selenocysteine insertion. Key Concepts Selenium is an essential trace element for many organisms including humans. The most important form of biologically active selenium is the amino acid selenocysteine. Selenocysteine is co‐translationally inserted into growing polypeptides. Selenocysteine insertion proceeds via a unique mechanism recoding UGA. The mechanism of selenocysteine insertion differs in Bacteria, Archaea, and Eukarya.