Selenocysteine

The structure of selenocysteine ​​is similar to that of cysteine ​​with the only difference being that the sulfur atom in it is replaced by a selenium atom, forming a selenol group deprotonated at physiological pH values. Proteins containing one or more selenocysteine ​​residues are called selenoproteins . They have catalytic activity due to the biochemical activity of selenocysteine, which is why they are called selenoenzymes . , which determine the nucleophilicity of the active site of selenocysteine, were found in selenozymes whose structure was described.

Selenocysteine ​​has a lower dissociation constant (5.47) than cysteine ​​and a higher reduction potential . Due to these properties, selenocysteine ​​is involved in proteins with antioxidant activity ^[4] .

Unlike other amino acids found in proteins, selenocysteine ​​does not have its own special codon in the genetic code ^[5] . In fact, it is specifically encoded by the UGA codon, which is usually a stop codon . Such a mechanism is called translational transcoding ^[6] , and its effectiveness depends on the synthesized selenoprotein and translation initiation factors ^[7] . If the cells live in the absence of selenium, then the translation of selenoprotein ends at the UGA codon, which leads to the formation of a “circumcised”, non-functional enzyme. The UGA codon encodes selenocysteine ​​if the sequence of the insertion of selenocysteine is present in the mRNA ( eng. SECIS element, SECIS ). The SECIS element can be determined by the characteristic nucleotide sequences and features of the secondary structure of mRNA in the region of this element. In bacteria, the SECIS element is located directly behind the UGA codon (in the same reading frame ) ^[8] . In archaea and eukaryotes, SECIS is located in the 3'-untranslated region ( Eng. 3 'untranslated region, 3' UTR ) and can force several UGA codons to encode selenocysteine ^[9] .

Another difference between selenocysteine ​​and standard amino acids is that it does not exist freely inside the cell, since its high reactivity can harm the cell. Instead, the cell stores selenium in the form of less active selenide (H ₂ Se). The synthesis of selenocysteine ​​is carried out on specialized tRNAs , which also include it in the growing peptide chain. The primary and secondary structure of selenocysteine-specific tRNAs, ^Sec tRNAs, differ from those of standard tRNAs in several aspects. So, the acceptor region contains 8 base pairs in bacteria and 10 in eukaryotes, a longer ; in addition, ^Sec tRNA is characterized by the replacement of several rather conservative base pairs. ^Sec tRNA is initially bound to serine using the seryl-tRNA ligase enzyme, however, the formed Ser-tRNA complex ^Sec does not enter into translation , because it is not recognized by normal translation factors (EF-Tu in bacteria and eEF1A in eukaryotes). The serine residue bound by tRNA is converted to the selenocysteine ​​residue by the pyridoxal- enzyme . Finally, the formed Sec-tRNA complex Sec specifically binds to an alternative translational factor (SelB or mSelB (or eEFSec)), which deliberately delivers it to the ribosome that translates mRNA for selenoprotein. The specificity of this delivery is due to the presence of an additional protein domain (in bacteria, SelB) or an additional subunit (SBP2 for eukaryotic mSelB / eEFSec), which binds to the corresponding element of the mRNA secondary structure formed by the SECIS element.

In humans, 25 selenoproteins are known ^[10] .

Derivatives of selenocysteine ​​γ-glutamyl-Se-methylselenocysteine ​​and Se-methylselenocysteine ​​are naturally known in plants of the genera of onions ( Allium ) and cabbage ( Brassica ) ^[11] .

Biotechnological applications of selenocysteine ​​include the use of Sec labeled with the ⁷³ Se isotope ( half-life of 7.2 hours) in positron emission tomography , as well as Sec containing ⁷⁵ Se (half-life of 118.5 days) for radioactive labeling. Single selenocysteine ​​or selenocysteine ​​in combination with selenomethionine (SeMet) to facilitate the determination phase using in protein x-ray diffraction analysis . It is possible to include the stable isotope ⁷⁷ Se, whose nuclear spin is ½, for high-resolution nuclear magnetic resonance ^[2] .

• Pyrrolysin , another non-standard amino acid.
• Selenomethionine , another selenium-containing amino acid that accidentally replaces methionine.
• Selenoproteins

• Lobanov AV, Hatfield DL, Gladyshev VN Eukaryotic selenoproteins and selenoproteomes // Biochimica et Biophysica Acta. - 2009. - Vol. 1790, No. 11 . - P. 1424-1428. - DOI : 10.1016 / j.bbagen.2009.05.05.014 .
• Turanov AA, Shpikalova MA, Lobanov AV, Fomenko DE, Morrison HG, Sogin ML, Klobutcher LA, Hatfield DL, Gladyshev VN Genetic code supports targeted insertion of two amino acids by one codon // Science . - 2009. - Vol. 323, no. 5911 . - P. 259-261. - DOI : 10.1126 / science.1164748 .
• Zinoni F., Birkmann A., Leinfelder W., Bock A. Cotranslational insertion of selenocysteine ​​into formate dehydrogenase from Escherichia coli directed by a UGA codon (English) // Proceedings of the National Academy of Sciences . - National Academy of Sciences , 1987. - Vol. 84, no. 10 . - P. 3156-3160. - DOI : 10.1073 / pnas.84.10.3156 . - PMID 3033637 .

• Unicellular has cast doubt on one of the fundamental tenets of genetics . Tape.ru , January 11, 2009 (Retrieved July 29, 2011)
• Peter Baranov. Codon in two faces . Gazeta.ru , January 12, 2009 (Retrieved July 29, 2011)
• Alexander Markov. The genetic code is ambiguous . Elements , January 14, 2009 (Retrieved July 29, 2011)