Seleno-cysteine

Another selenium-containing molybdenum hydroxylase that has been isolated from Clostridium barkeri (identical to Eubacterium barkeri) is nicotinic acid hydroxylase (NAH). Clostridium barkeri was isolated initially as a fermentor of nicotinic acid and thus NAH is a key enzyme in the efficient fermentation of nicotinic acid as a source of carbon and energy. NAH contained selenium when purified from cells labeled with Se-selenite. However, this label was lost during denaturing gel electrophoresis and also on heating of the enzyme (Dilworth 1982). Exhaustive analysis of selenium-labeled alkylation products of NAH under various conditions revealed selenium was bound as a labile cofactor (Dilworth 1982), and not as seleno-cysteine. This report was the first to describe a selenium-dependent enzyme that did not contain selenium in the form of selenocysteine. 

Strub, M. R, et al. (2003). Selenomethionine and seleno-cysteine double labeling strategy for crystallographic phasing. Structure (Camb) 11,1359-1367. 

In humans, the major pathway in the metabolism of the thyroid hormones consists of the removal of iodine or deiodination. Three deiodinase isoenzymes, encoded on three distinct genes, catalyze the reductive deiodination. All three enzymes contain the rare amino acid seleno-cysteine. The essential trace element selenium therefore plays an important role in thyroid hormone economy. 

Se Speciation in Plants The presence of a number of volatile Se species was reported in edible allium plants such as garlic by GC-AES [79]. Selenomethionine, Se-methylselenocysteine, and y-glutamyl-Se-methyl-L-seleno cysteine were identibed in garlic and onion by HPLC-ICP-MS and ES-MS/MS [80]. Selenomethionine is the primary species found in all types of nuts (19D25 percent of the total Se) [30], sunBower [81], and mushrooms [36, 37], The distribution of Se among different fractions (lipid extract, low molecular weight, and protein fractions) of nuts and speciation analysis was studied [30]. Selenium was not detected in any of the lipid extracts obtained from the different types of nuts [30], Results obtained for Brazil nuts by SEC with on-line ICP-MS detection showed that approximately 12 percent of total Se was weakly bound to proteins [30],... 

Boyington, J. C., Gladyshev, V. N., Khangulov, S. V., Stadtman,T. C., and Sun, P. D., 1997, Crystal stmcture of formate dehydrogenase H catalysis involving Mo, molybdopterin, seleno-cysteine and an Fe cluster, Science 275 1305nl308. 

In 1986 scientists found a 21st amino acid, seleno-cysteine. In 2002 two teams of researchers from Ohio State University identified the 22nd genetically encoded amino acid, called pyrrolysine, a discovery that is the... 

Cys desulfurases were also reported to catalyze the decomposition of selenocysteine to L-alanine and elemental selenium with varying efficiency. The catalytic mechanism of both cysteine desulfuration and selenocysteine deselenation is similar. The PLP-binding Lys is the base that accepts the Ca proton of the substrate and reprotonates the intermediate to form a ketimine species. The selenohydryl group of L-seleno-cysteine is probably deprotonated and present in an anionic form. The deprotonation of the selenohydryl group may be facilitated by a His residue, located in the active site. The Cys residue is not essential for deselenation process. Selenium is, then, released spontaneously from the ketimine intermediate. ... 

Selenium substitutes for sulfur in amino acids to form seleno-cysteine, cystine, and methionine. The selenium-containing antioxidant glutathione peroxidase is biologically important, and selenium is a necessary trace nutrient in warm-blooded animals. Grazing animals develop a form of muscular dystrophy and other disorders when grazing in areas in which the selenium has been depleted with selenium-depleted diets, people develop... 

Fu L-H, Wang X-F, Eyal Y, She Y-M, Donald LJ, Standing KG and Ben-Hayyim G (2002) A selenoprotein in the plant kingdom mass spectrometry conforms that opal codon (UGA) encodes seleno-cysteine in Ghlamydomonas reingardtii glutathione peroxidase. J Biol Chem 277 25983-25991. 

JC Boyington, VN Gladyshev, SV Khangulov, TC Stadtman, PD Sun. Crystal structure of formate dehydrogenase H Catalysis involving Mo, molybdopterin, seleno-cysteine, and an Fe4S4 cluster. Science 275 1305-1308, 1997. 

Table 3.2 is a listing of the one-letter symbols, the three-letter symbols, and the chemical properties of the side chains of the standard amino acids (Table 3.3) [8]. The masses listed are based on weighted averages of the elemental isotopes at their natnral abnndances. Note that forming a peptide bond results in the elimination of a molecule of water, so the mass of an amino acid unit within a protein chain is reduced by 18.01524Da. The one-letter symbol for an undetermined amino add is X. The three-letter symbol Asx or one-letter symbol B means the amino acid is either asparagine or aspartic acid Glx or Z means either glutamic acid or glutamine and Xle or J means either leucine or isoleucine. The lUPAC and lUBMB [9] now also recommend that Sec or U refers to seleno-cysteine, and Pyl or 0 refers to pyrrolysine.

Nigam, S. N., J. Tu, and W. B. McConnell Distribution of selenomethyl-seleno-cysteine and some other amino acids in species of Astragalus, with special reference to their distribution during the growth of A. hisulcatus. Phytochemistry 8, 1161 (1969). 

The nickel-containing hydrogenases can be classified in two different categories, differing by ligation of the [NiFe]-cluster found in the active site to either cysteine or seleno-cysteine. 

An interesting example of the use of MCRs on water is the synthesis of seleno cysteines by the Ugi reaction developed by Wessjohann and coworkers [74]. The reactions of seleno-derived aldehydes 123 with amines 9, carboxylic acids 125, and isocyanides 124 afforded the corresponding seleno amino acids 126 in variable yields (24-87%) (Scheme 11.24). 

SCHEME 11.24 Synthesis of seleno cysteines 126 reported by Wessjohann. 

One of the nonsense codons, UGA, has an additional function in the synthesis of selenoproteins. The process involves the initial synthesis of selenocysteyl-tRNA from a novel seryl-tRNA and selenium. This tRNA contains an anticodon that is able to decode UGA and insert seleno-cysteine residues into the growing polypeptide chain, but... 

The model study of the inactivation of GPx by nitrosating agents was then examined. It was proposed that the inactivation of GPx by an 5-nitrosothiol proceeds by a two-step mechanism (Scheme 11.27). The first step is 5 e-nitrosation of seleno-cysteine to produce the 5e-nitrososeIenoI intermediate that can be reduced to the active form by treatment with DTT. The second step involves the formation of an interbridge selenenyl sulfide and cannot be reversed by a reducing agent. 

As mentioned above, Zn is the most abundant transition metal in cells, and plays a vital role in the functionalities of more than 300 enzymes, in the stabilization of DNA, and in gene expression. Other trace metals, such as Se, W, and Mo, are essential in human health and also important in the environment. For example, Se is usually incorporated into antioxidant enzymes as seleno-cysteine (SeCys), the redox active site of SeCys-containing enzymes, and plays a key role in host oxidative defense. It is predicted that there are a total of 25 SeCys-containing proteins in humans. The most widely known SeCys-containing enzymes are thioredoxin reductase and glutathione peroxidase. Both are ubiquitous and found in bacteria, plants, and mammals, including humans. ... 

Selenoproteome The part of the proteome incorporating sele-noamino acids, selenomethionine and seleno-cysteine. The use of the term is often limited to proteins with genetically encoded selenocys-teine only 17... 

Plants can assimilate inorganic selenium into selenium isol( of organic sulfur compounds. This involves nonspecific incorporation of selenium in place of sulfur, as distinct from the selenium-specific incorporation of seleno-cysteine into the peptide linkage of selenoproteins such as GSH peroxidase in animals. This subject has been reviewed by Anderson and Scarf (1983) and Brown and Shrift (1982) and only an outline of the processes involved is given here. 

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