Selenocysteine Incorporation Machinery and the Role of Selenoproteins in Development and Health

The pathway to GTPase activation of elongation factor SelB on the ribosome

“…Sec has unique chemical properties, which make it an essential residue in the active site of key redox enzymes in all domains of life 2 . Defects in Sec biosynthesis and selenoprotein malfunction have been linked to an increasing number of diseases in humans 12 . Sec incorporation into non-selenoproteins, as well as the exploitation of the Sec machinery to insert designer amino acids, has received growing interest for biotechnological applications 13,14 .…”

New Developments in Selenium Biochemistry: Selenocysteine Biosynthesis in Eukaryotes and Archaea

“…Several thorough reviews have covered these topics [1][2][3][4]. Herein, we have focused on recent developments involving the biosynthesis of selenocysteine (Sec) in eukaryotes and archaea that have not been reviewed elsewhere.…”

“…It is cotranslationally inserted into protein in response to the codon, UGA [1][2][3][4]. The biosynthesis of Sec occurs on its transfer RNA (tRNA), and the pathway begins with the initial aminoacylation of Sec tRNA with serine [5,6].…”

“…The kinase, designated O-phosphoseryl-tRNA [Ser]Sec kinase (PSTK), was recently isolated, characterized, and found to specifically phosphorylate the seryl moiety on seryl-tRNA [Ser]Sec [18]. The resulting O-phosphoseryltRNA [Ser]Sec product had been proposed as an intermediate in the biosynthesis of Sec [3,18]. In addition, because no sequences with homology to SelA could be detected in eukaryotes, there was some question as to the identity of the Sec synthase (SecS) in mammals.…”

“…In addition, because no sequences with homology to SelA could be detected in eukaryotes, there was some question as to the identity of the Sec synthase (SecS) in mammals. The soluble liver antigen (SLA), which was initially identified as a 48-kDa protein bound to Sec tRNA [Ser]Sec and was targeted by antibodies in patients with an autoimmune chronic hepatitis [19], was reported to occur as a separate family within a larger superfamily of diverse PLP-dependent transferases [20] and proposed as a possible SecS in mammals [3,[20][21][22]. SLA was also found to exist in a protein complex with other factors involved in Sec biosynthesis and/or its insertion into protein providing further evidence that this protein is involved in selenium metabolism [22,23].…”