Selenocysteine: the 21st amino acid.

See its structure
Böck A, Forchhammer K, Heider J, Leinfelder W, Sawers G, Veprek B, Zinoni F.Lehrstuhl für Mikrobiologie, Universität München, Germany.

Great excitement was elicited in the field of selenium biochemistry in 1986 by the parallel discoveries that the genes encoding the selenoproteins glutathione peroxidase and bacterial formate dehydrogenase each contain an in-frame TGA codon within their coding sequence. We now know that this codon directs the incorporation of selenium, in the form of selenocysteine, into these proteins. Working with the bacterial system has led to a rapid increase in our knowledge of selenocysteine biosynthesis and to the exciting discovery that this system can now be regarded as an expansion of the genetic code. The prerequisites for such a definition are co-translational insertion into the polypeptide chain and the occurrence of a tRNA molecule which carries selenocysteine. Both of these criteria are fulfilled and, moreover, tRNASec even has its own special translation factor which delivers it to the translating ribosome. It is the aim of this article to review the events leading to the elucidation of selenocysteine as being the 21st amino acid. Gene for a novel tRNA species that accepts L-serine and cotranslationally inserts selenocysteine.
Leinfelder W, Zehelein E, Mandrand-Berthelot MA, Böck A. Institut für Genetik und Mikrobiologie, Universität München, FRG.

The biological requirement of the trace element selenium was recognized 40 years ago. Selenium is incorporated into several enzymes and transfer RNA species of both prokaryotic and eukaryotic origin. In enzymes which contain a selenopolypeptide, selenium is present as covalently bound selenocysteine which participates in the catalytic reaction. Sequence analysis of the genes coding for two selenoproteins, formate dehydrogenase H from Escherichia coli and glutathione peroxidase from mouse and man, demonstrated that an in-frame UGA opal nonsense codon directs the incorporation of selenocysteine. In the case of formate dehydrogenase incorporation occurs cotranslationally. Recently, we identified four genes whose products are required for selenocysteine incorporation in E. coli. We report here that one of these genes codes for a tRNA species with unique properties. It possesses an anticodon complementary to UGA and deviates in several positions from sequences, until now, considered invariant in all tRNA species. This

tRNA is aminoacylated with L-serine by the seryl-tRNA ligase which also charges cognate tRNASer. Selenocysteine, therefore, is synthesized from a serine residue bound to a natural suppressor tRNA which recognizes UGA. Identification of a novel translation factor necessary for the incorporation of selenocysteine into protein. Forchhammer K, Leinfelder W, Böck A. Lehrstuhl für Mikrobiologie der Universität, München, FRG. During the biosynthesis of selenoproteins in both prokaryotes and eukaryotes, selenocysteine is cotranslationally incorporated into the nascent polypeptide chain through a process directed by a UGA codon that normally functions as a stop codon. Recently, four genes have been identified whose products are required for selenocysteine incorporation in Escherichia coli. One of these genes, selC, codes for a novel transfer RNA species (tRNAUCA) that accepts serine and cotranslationally inserts selenocysteine by recognizing the specific UGA codon. The serine residue attached to this tRNA is converted to selenocysteine in a reaction dependent on functional selA and selD gene products. By contrast, the selB gene product (SELB) is not required until after selenocysteyl-tRNA biosynthesis. Here we present evidence indicating that SELB is a novel translation factor. The deduced amino-acid sequence of SELB exhibits extensive homology with the sequences of the translation initiation factor-2 (IF-2) and elongation factor Tu (EF-Tu). Furthermore, purified SELB protein binds guanine nucleotides in a 1:1 molar ratio and specifically complexes selenocysteyl-tRNAUCA, but does not interact with seryltRNAUCA. Thus, SELB could be an amino acid-specific elongation factor, replacing EF-Tu in a special translational step. For More information on Recent Trends in Biochemistry visit my web page at Biochemistry Online