The Molecular Mechanism of the Synthesis of the 21st Amino Acid, Selenocysteine

Abstract

Selenocysteine (Sec) is the 21st amino acid that is incorporated into proteins translationally. The selenocysteine tRNA (tRNA^Sec) is first ligated with serine by seryl-tRNA synthetase, and the Ser moiety is converted to Sec in a tRNA-dependent manner. In Bacteria, the selenocysteine synthase SelA converts Ser to Sec directly, whereas in Eukaryotes and Archaea, phosphorylation of the Ser moiety is required prior to the Sec conversion. In this review, we describe the crystal structures of SelA, bacterial tRNA^Sec, and the SelA•tRNA^Sec complex. Based on the crystal structures and mutational analyses, the substrate discrimination and reaction mechanisms are discussed.