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Selenocysteine (Sec, U), shown at right ( ), is called the 21st amino acid[1]. It is incorporated into rare proteins in all domains of life, and is essential for life. When the UGA stop codon is accompanied by a suitable signal, it is translated as Sec instead of stopping translation. In the PDB, the code for hetero group Sec is CSE. For more information beyond what is below, please see Selenocysteine in Wikipedia.



Knockout of tRNASec in mice causes embryonic lethality[2]. This seems to fit with the occurrence of Sec in several important enzymes.


Sec occurs in all domains of life, including bacteria, archaea, and eukaryota[3][4]. Sec occurs in the active sites of enzymes involved in removing reactive oxygen species, and in thyroid hormone activation[2]. For more examples, please see Selenocysteine in Wikipedia.

HIC-Up reports the occurrence of Sec in 11 entries in the PDB. The highest resolution entry is 1kqf (1.6 Å), with Sec at 196 in chain A. To see it, go to 1kqf and click on CSE under Non-Standard Residues.

Translation from UGA Stop Codon

During translation of mRNA, UGA is normally interpreted as a stop codon. However, when a special Sec-insertion sequence (SECIS), a stem-loop structure, is present downstream (in the untranslated region in mammals), UGA is translated as Sec[1][2]. This involves the interaction of this stem-loop structure with specialized elongation factors called SelB in bacteria and EFSec in humans[2].

Structure and Synthesis

Cysteine (Cys) has a sulfur-containing side chain -CH2-SH. In selenocysteine, the sulfur is replaced with selenium, making the side chain -CH2-SeH. However, as explained below, Sec is not synthesized from Cys, but rather from Ser (sidechain -CH2-OH), by the replacement of oxygen with selenium.

Sec differs from the 20 standard amino acids because, in all domains of life, it lacks its own tRNA synthetase, and is synthesized from Ser covalently linked to tRNASec.

The crystal structure of the complex that converts Ser-tRNASec to Sec-tRNASec (3hl2) was reported in 2009[2]. This consists of O-Phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) complexed to tRNASec, phosphoserine, and thiophosphate. The authors conclude that this structure, together with enzymology, supports a pyridoxal phosphate-dependent mechanism.

Notes and References

  1. 1.0 1.1 Atkins JF, Gesteland RF. The twenty-first amino acid. Nature. 2000 Sep 28;407(6803):463, 465. PMID:11028985 doi:10.1038/35035189
  2. 2.0 2.1 2.2 2.3 2.4 Palioura S, Sherrer RL, Steitz TA, Soll D, Simonovic M. The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation. Science. 2009 Jul 17;325(5938):321-5. PMID:19608919 doi:325/5938/321
  3. Lobanov AV, Hatfield DL, Gladyshev VN. Eukaryotic selenoproteins and selenoproteomes. Biochim Biophys Acta. 2009 Nov;1790(11):1424-8. Epub 2009 May 27. PMID:19477234 doi:10.1016/j.bbagen.2009.05.014
  4. Selenocysteine in Wikipedia

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