SelenocysteinSynthase

SelenocysteinSynthase is a PLP-dependent enzyme involved in the biosynthesis of selenocysteine, the 21st amino acid, on its transfer RNA. In bacteria, this enzyme is commonly known as SelA and converts Ser-tRNA[Sec] directly into Sec-tRNA[Sec] using selenophosphate as the selenium donor. In archaea and eukaryotes, a related enzyme called SepSecS performs a similar function later in the pathway, converting phosphoserine-containing tRNA[Sec] to Sec-tRNA[Sec] with selenium supplied by selenophosphate. The resulting Sec-tRNA[Sec] is then used by the ribosome to insert selenocysteine at in-frame UGA codons in the presence of appropriate translation factors and RNA elements.

The activity of SelenocysteinSynthase depends on the availability of selenium and the tRNA[Sec] substrate. In bacterial systems, SelA collaborates with SelD to access selenophosphate and with SelB, a specialized translation elongation factor that guides Sec-tRNA[Sec] to the ribosome at Sec-decoding sites. In archaea and eukaryotes, SepSecS works within a distinct Sec incorporation apparatus that includes SepCysSec and other factors, alongside the Sec decoding machinery and SECIS elements in the mRNA.

Biological significance arises from the role of selenocysteine in many redox-active enzymes, such as certain peroxidases and deiodinases. Organisms that synthesize selenoproteins rely on SelenocysteinSynthase to supply Sec-tRNA[Sec] for accurate codon reassignment during translation. Loss or inactivation of this pathway can prevent Sec incorporation and lead to reliance on cysteine substitutions. See also selenocysteine, selenophosphate synthetase, and selenoprotein biosynthesis.