Selenocysteine
Selenocysteine (symbol Sec or U, in older publications also as Se-Cys) is the 21st proteinogenic amino acid. Selenoproteins contain selenocysteine residues. Selenocysteine is an analogue of the more common cysteine with selenium in place of the sulfur. Selenocysteine is present in several enzymes (for example glutathione peroxidases, tetraiodothyronine 5′ deiodinases, thioredoxin reductases, formate dehydrogenases, glycine reductases, selenophosphate synthetase 2, methionine-"R"-sulfoxide reductase B1 (SEPX1), and some hydrogenases). It occurs in all three domains of life. Selenocysteine was discovered by biochemist Thressa Stadtman at the National Institutes of Health. Chemistry. Selenocysteine is the Se-analogue of cysteine. It is rarely  encountered (and not available commercially) because it is very susceptible to air-oxidation. More common is the oxidized derivative selenocystine, which has an Se-Se bond. Both selenocysteine and Selenocystine are white solids. The Se-H group is more acidic (p"K" = 5.43) than the thiol group, thus it is deprotonated at physiological pH. Structure. Selenocysteine has a structure similar to that of cysteine, but with an atom of selenium taking the place of the usual sulfur. It has a selenol group. Like other natural proteinogenic amino acids, cysteine and selenocysteine have chirality in the older / notation based on homology  to - and -glyceraldehyde. In the newer "R"/"S" system of designating chirality, based on the atomic numbers of atoms near the asymmetric carbon, they have "R" chirality, because of the presence of sulfur or selenium as a second neighbor to the asymmetric carbon. The remaining chiral amino acids, having only lighter atoms in that position, have "S" chirality.) Proteins which contain a selenocysteine residue are called selenoproteins. Most selenoproteins contain a single selenocysteine residue. Selenoproteins that exhibit catalytic activity are called selenoenzymes. Biology. Selenocysteine has a lower reduction potential than cysteine. These properties make it very suitable in proteins that are  involved in antioxidant activity. Although it is found in the three domains of life, it is not universal in all organisms. Unlike other amino acids present in biological proteins, selenocysteine is not coded for directly in the genetic code. Instead, it is encoded in a special way by a UGA codon, which is normally the "opal" stop codon. Such a mechanism is called translational recoding and its efficiency depends on the selenoprotein being synthesized and on translation initiation factors. When cells are grown in the absence of selenium, translation of selenoproteins terminates at the UGA codon, resulting in a truncated , nonfunctional enzyme. The UGA codon is made to encode selenocysteine by the presence of a selenocysteine insertion sequence (SECIS) in the mRNA. The SECIS element is defined by characteristic nucleotide sequences and secondary structure base-pairing patterns. In bacteria, the SECIS element is typically located immediately following the UGA codon within the reading frame for the selenoprotein. In Archaea and in eukaryotes, the SECIS element is in the 3′ untranslated region (3′ UTR) of the mRNA and can direct multiple UGA codons to encode selenocysteine residues. Unlike the other amino acids, no free pool of selenocysteine exists in the cell . Its high reactivity would cause damage to cells. Instead, cells store selenium in the less reactive oxidized form, selenocystine, or in methylated form, selenomethionine. Selenocysteine synthesis occurs on a specialized tRNA, which also functions to incorporate it into nascent polypeptides. The primary and secondary structure of selenocysteine-specific tRNA, tRNA, differ from those of standard tRNAs in several respects, most notably in having an 8-base-pair (bacteria) or 10-base-pair (eukaryotes) acceptor stem, a long variable region arm, and substitutions at several well-conserved base positions. The selenocysteine tRNAs are initially charged with serine by seryl-tRNA ligase , but the resulting Ser-tRNA is not used for translation because it is not recognised by the normal translation elongation factor (EF-Tu in bacteria, eEF1A in eukaryotes). Rather, the tRNA-bound seryl residue is converted to a selenocysteine residue by the pyridoxal phosphate-containing enzyme selenocysteine synthase. In eukaryotes and archaea, two enzymes are required to convert tRNA-bound seryl residue into tRNA selenocysteinyl residue: PSTK ("O"-phosphoseryl-tRNA[Ser]Sec kinase) and selenocysteine synthase. Finally, the resulting Sec-tRNA is specifically bound to an alternative translational elongation factor (SelB or mSelB (or eEFSec)), which delivers it in a targeted manner to  the ribosomes translating mRNAs for selenoproteins. The specificity of this delivery mechanism is brought about by the presence of an extra protein domain (in bacteria, SelB) or an extra subunit (SBP2 for eukaryotic mSelB/eEFSec) which bind to the corresponding RNA secondary structures formed by the SECIS elements in selenoprotein mRNAs. Selenocysteine is decomposed by the enzyme selenocysteine lyase into -alanine and selenide. , 136 human proteins (in 37 families) are known to contain selenocysteine (selenoproteins). Selenocysteine derivatives γ-glutamyl-"Se"-methylselenocysteine and "Se"-methylselenocysteine occur naturally in plants of the genera "Allium" and "Brassica". Applications. Biotechnological applications of selenocysteine include use of Se -labeled Sec (half-life of Se = 7.2 hours) in positron emission tomography (PET) studies and Se-labeled Sec (half-life of Se = 118.5 days) in specific radiolabeling, facilitation of phase determination by multiwavelength anomalous diffraction in X-ray crystallography of proteins by introducing Sec alone, or Sec together with selenomethionine (SeMet), and incorporation of the stable Se isotope, which has a nuclear spin of and can be used for high-resolution NMR, among others.