Selenocysteine

• Selenocysteine

• L- selenocysteine
• (R)- selenocysteine
• D- selenocysteine
• ( S)- selenocysteine
• DL- selenocysteine
• ( RS)- selenocysteine
• L-2- amino-3- hydroselenopropansäure
• Abbreviations: Sec ( Three letter code)
• U ( single letter code )

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L- selenocysteine ​​(abbr. Sec or U) is the 21 proteinogenic L- amino acid and a reactive analogue of the natural L- cysteine. Contains selenocysteine ​​instead of the sulfur atom, a selenium atom. D- selenocysteine ​​is enantiomeric to L- selenocysteine ​​and has only minor importance. If in this article or in the scientific literature, the configuration is not specified, is " selenocysteine ​​" always for L- selenocysteine ​​.

Properties

L- selenocysteine ​​[ Synonym: (R)- selenocysteine ​​] is related chemically closely with the amino acid L-cysteine, however, has a lower acid constant pK a = 5.3 of the selenol in comparison with pK a = 8-10 for the thiol group of the L - cysteine. Also selenocysteine ​​redox-active than cysteine. These properties are likely to be a major reason for the incorporation of L- selenocysteine ​​in enzymes. Selenocysteine ​​is present predominantly as an inner salt or zwitterion, whose formation can be explained by the fact that the proton of the carboxyl group migrates to the lone electron pair of the nitrogen atom of the amino group:

In an electric field, the zwitterion migrates not because it is not loaded as a whole. Strictly speaking, this is at the isoelectric point ( at a certain pH value) of the case where the selenocysteine ​​also has its lowest solubility in water.

Biochemistry

The genetic code applies in principle to all major forms of life, however there are some peculiarities. While the default code allows the cells to produce proteins from the known 20 α -amino acids, bacteria, archaea and eukaryotes can install via a mechanism known as recoding selenocysteine ​​during translation. The incorporation of L- selenocysteine ​​often allows only the operability of many essential enzymes.

Occurrence

It is known today about 30 and more than 15 -bacterial eukaryotic selenocysteine ​​-containing proteins. As occur in mammals, inter alia, various glutathione peroxidases tetraiodothyronine - deiodinases or large thioredoxin reductases in bacteria and archaea and formate dehydrogenase, hydrogenase, protein components of the glycine reductase and D -proline reductase systems and more enzymes of the metabolic pathway of methane formation as selenocysteinhaltige enzymes in appearance.

Many of these enzymes mediate redox reactions. In them, the reactive selenocysteine ​​in the active center. Of particular importance for eukaryotes has glutathione peroxidase as a member of a cellular " defense brigade " against the consequences of oxidative stress. Disturbances in the function of these selenoproteins are associated with syndromes such as Keshan and Kashin - Beck disease and may play a role in tumor formation and atherosclerosis.

Biosynthesis

Biosynthetically produced L- selenocysteine ​​as follows (see figure):

• Binding of the α - amino acid is L -serine (Ser) to a specific tRNA ( tRNASec ) with the anticodon UCA.
• This is tRNASec selenyliert, i.e., the L-serine is converted to L- selenocysteine ​​( Sec), by the hydroxy group of the side chain is replaced by selenol ( SeH ). This creates the Sec - tRNASec.

The Sec - tRNASec has the anticodon UCA and pairs with the codon UGA mRNA. Normally, the codon UGA ( opal stop codon ) causes the termination of translation. However, the mRNA forms a hairpin structure, the stop codon UGA is ignored and the selenocysteine ​​can be incorporated into the protein. This process is also referred to as re-encoding.

In bacteria, there is such a SECIS ( selenocysteine ​​insertion sequence) called sequence of the mRNA in the immediate vicinity of the UGA codon. In eukaryotes and archaea, this sequence is further away on the mRNA from the UGA codon.

The incorporation of L- selenocysteine ​​into the protein in bacteria is as follows (see also the figure):

• The simultaneous presence of sec- tRNASec and SECIS sequence is recognized by a specific, GTP - dependent translation factor, elongation factor Selb. In the picture of this translation factor is shown as a green sphere.
• The reinterpretation of the codon UGA is now possible and that selenocysteine ​​can be incorporated into the protein. Another UGA stop codon ( in the figure marked as STOP ) terminates translation.

In eukaryotes, the function of the bacterial translation factor Seib is divided into two proteins: the so-called mSelB binds the charged tRNA and the GTP and brings it to the ribosome. The so-called SBP2 recognizes and binds the SECIS sequence of eukaryotic mRNAs.

The ratios in the Selenoproteinsynthese the Archaea are not yet elucidated.