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Journal of the American Chemical Society Jul 2023The -nitrosation in selenoproteins such as glutathione peroxidase and thioredoxin reductase to produce -nitrososelenocysteines (Sec-SeNOs) has been proposed to play...
The -nitrosation in selenoproteins such as glutathione peroxidase and thioredoxin reductase to produce -nitrososelenocysteines (Sec-SeNOs) has been proposed to play crucial roles in signaling processes mediated by reactive nitrogen species and nitrosative-stress responses, although chemical evidence for the formation of Sec-SeNOs has been elusive not only in proteins but also in small-molecule systems. Herein, we report the first synthesis of a Sec-SeNO by employing a selenocysteine model system that bears a protective molecular cradle. The Sec-SeNO was characterized using H and Se nuclear magnetic resonance as well as ultraviolet/visible spectroscopy and found to have persistent stability at room temperature in solution. The reaction processes involving the Sec-SeNO provide experimental information that serves as a chemical basis for elucidating the reaction mechanisms involving the SeNO species in biological functions, as well as in selenol-catalyzed NO generation from -nitrosothiols.
Topics: Nitrosation; Selenoproteins; Glutathione Peroxidase; Thioredoxin-Disulfide Reductase; Selenocysteine; Selenium
PubMed: 37267591
DOI: 10.1021/jacs.3c03394 -
Plants (Basel, Switzerland) Jan 2024An in-depth understanding of Se uptake and metabolism in plants is necessary for developing Se biofortification strategies. Thus, hydroponic experiments were conducted...
An in-depth understanding of Se uptake and metabolism in plants is necessary for developing Se biofortification strategies. Thus, hydroponic experiments were conducted to investigate the associated processes and mechanisms of organic Se (selenomethionine (SeMet) and selenomethionine-oxide (SeOMet)) uptake, translocation, transformation and their interaction in wheat, in comparison to inorganic Se. The results showed that Se uptake by the roots and the root-to-shoot translocation factor under the SeMet treatment were higher than those under the selenite, selenate and SeOMet treatments. The uptake and translocation of SeMet were higher than those of SeOMet within 72 h, although the differences gradually narrowed with time. The uptake of SeMet and SeOMet was also sensitive to the aquaporin inhibitor: AgNO addition resulted in 99.5% and 99.9% inhibitions of Se in the root in the SeMet and SeOMet treatments, respectively. Once absorbed by the root, they rapidly assimilated to other Se forms, and SeMet and Se-methyl-selenocysteine (MeSeCys) were the dominant species in SeMet- and SeOMet-treated plants, while notably, an unidentified Se form was also found in the root and xylem sap under the SeMet treatment. In addition, within 16 h, SeOMet inhibited the uptake and translocation of SeMet, while the inhibition was weakened with longer treatment time. Taken together, the present study provides new insights for the uptake and transformation processes of organic Se within plants.
PubMed: 38337913
DOI: 10.3390/plants13030380 -
Poultry Science May 2024As one of the indispensable trace elements for both humans and animals, selenium widely participates in multiple physiological processes and facilitates strong... (Review)
Review
As one of the indispensable trace elements for both humans and animals, selenium widely participates in multiple physiological processes and facilitates strong anti-inflammatory, antioxidant, and immune enhancing abilities. The biological functions of selenium are primarily driven by its presence in selenoproteins as a form of selenocysteine. Broilers are highly sensitive to selenium intake. Recent reports have demonstrated that selenium deficiency can adversely affect the quality of skeletal muscles and the economic value of broilers; the regulatory roles of several key selenoproteins (e.g., GPX1, GPX4, TXNRD1, TXNRD3, SelK, SelT, and SelW) have been identified. Starting from the selenium metabolism and its biological utilization in the skeletal muscle, the effect of the selenium antioxidant function on broiler meat quality is discussed in detail. The progress of research into the prevention of skeletal muscle injury by selenium and selenoproteins is also summarized. The findings emphasize the necessity of in vivo and in vitro research, and certain mechanism problems are identified, which aids their further examination. This mini-review will be helpful to provide a theoretical basis for the further study of regulatory mechanisms of selenium nutrition in edible poultry.
Topics: Animals; Selenium; Chickens; Muscle, Skeletal; Selenoproteins; Animal Feed; Diet; Animal Nutritional Physiological Phenomena
PubMed: 38520938
DOI: 10.1016/j.psj.2024.103646 -
Current Research in Structural Biology 2024The 21st amino acid, selenocysteine (Sec), is synthesized on its dedicated transfer RNA (tRNA). In bacteria, Sec is synthesized from Ser-tRNA by Selenocysteine Synthase...
The 21st amino acid, selenocysteine (Sec), is synthesized on its dedicated transfer RNA (tRNA). In bacteria, Sec is synthesized from Ser-tRNA by Selenocysteine Synthase (SelA), which is a pivotal enzyme in the biosynthesis of Sec. The structural characterization of bacterial SelA is of paramount importance to decipher its catalytic mechanism and its role in the regulation of the Sec-synthesis pathway. Here, we present a comprehensive single-particle cryo-electron microscopy (SPA cryoEM) structure of the bacterial SelA with an overall resolution of 2.69 Å. Using recombinant SelA, we purified and prepared samples for single-particle cryoEM. The structural insights from SelA, combined with previous and knowledge, underscore the indispensable role of decamerization in SelA's function. Moreover, our structural analysis corroborates previous results that show that SelA adopts a pentamer of dimers configuration, and the active site architecture, substrate binding pocket, and key K295 catalytic residue are identified and described in detail. The differences in protein architecture and substrate coordination between the bacterial enzyme and its counterparts offer compelling structural evidence supporting the independent molecular evolution of the bacterial and archaea/eukarya Ser-Sec biosynthesis present in the natural world.
PubMed: 38681238
DOI: 10.1016/j.crstbi.2024.100143 -
Chemistry (Weinheim An Der Bergstrasse,... Aug 2023Diselenide-selenoester ligations are increasingly used for the synthesis of proteins. Excellent ligation rates, even at low concentrations, in combination with mild and...
Diselenide-selenoester ligations are increasingly used for the synthesis of proteins. Excellent ligation rates, even at low concentrations, in combination with mild and selective deselenization conditions can overcome some of the most severe challenges in chemical protein synthesis. Herein, the versatile multicomponent synthesis and application of a new ligation auxiliary that combines a photocleavable scaffold with the advantages of selenium-based ligation strategies are presented. Its use was investigated with respect to different ligation junctions and describe a novel para-methoxybenzyl deprotection reaction for the selenol moiety. The glycine-based auxiliary enabled successful synthesis of the challenging target protein G-CSF.
Topics: Peptides; Proteins
PubMed: 37265454
DOI: 10.1002/chem.202301253 -
Genome Biology and Evolution Mar 2024Selenocysteine, the 21st amino acid specified by the genetic code, is a rare selenium-containing residue found in the catalytic site of selenoprotein oxidoreductases....
Selenocysteine, the 21st amino acid specified by the genetic code, is a rare selenium-containing residue found in the catalytic site of selenoprotein oxidoreductases. Selenocysteine is analogous to the common cysteine amino acid, but its selenium atom offers physical-chemical properties not provided by the corresponding sulfur atom in cysteine. Catalytic sites with selenocysteine in selenoproteins of vertebrates are under strong purifying selection, but one enzyme, glutathione peroxidase 6 (GPX6), independently exchanged selenocysteine for cysteine <100 million years ago in several mammalian lineages. We reconstructed and assayed these ancient enzymes before and after selenocysteine was lost and up to today and found them to have lost their classic ability to reduce hydroperoxides using glutathione. This loss of function, however, was accompanied by additional amino acid changes in the catalytic domain, with protein sites concertedly changing under positive selection across distant lineages abandoning selenocysteine in glutathione peroxidase 6. This demonstrates a narrow evolutionary range in maintaining fitness when sulfur in cysteine impairs the catalytic activity of this protein, with pleiotropy and epistasis likely driving the observed convergent evolution. We propose that the mutations shared across distinct lineages may trigger enzymatic properties beyond those in classic glutathione peroxidases, rather than simply recovering catalytic rate. These findings are an unusual example of adaptive convergence across mammalian selenoproteins, with the evolutionary signatures possibly representing the evolution of novel oxidoreductase functions.
Topics: Animals; Selenocysteine; Cysteine; Selenium; Selenoproteins; Glutathione Peroxidase; Amino Acids; Glutathione; Sulfur; Mammals
PubMed: 38447079
DOI: 10.1093/gbe/evae041 -
Animal Nutrition (Zhongguo Xu Mu Shou... Mar 2024The production of selenium-enriched fish can contribute to alleviating selenium deficiency in human diets. However, it is still unclear which selenium source, as an...
The production of selenium-enriched fish can contribute to alleviating selenium deficiency in human diets. However, it is still unclear which selenium source, as an additive, can efficiently and cost-effectively produce high-quality selenium-enriched fish. This study evaluated the effects of selenium nanoparticles (SeNP), selenite, and selenomethionine (SeMet) on the growth, antioxidant capacity, selenium content, selenium speciation, and meat quality of grass carp. Ten diets were prepared, including a basal diet (BD) and three concentrations (0.1, 0.3, and 0.9 mg/kg) of SeNP, selenite, and SeMet. A total of 600 fish (250.79 ± 1.57 g) were randomly assigned to 30 tanks (3 tanks/group). Fish were fed the experimental diet three times daily for 60 d. In this study, SeNP most significantly promoted the growth and antioxidant capacity of grass carp, with 0.3 mg/kg SeNP identified as the optimal additive concentration. Additionally, SeNP demonstrated equally excellent bioavailability as SeMet and significantly increased the content of SeMet in grass carp () muscle. Furthermore, compared to SeMet and selenite, dietary SeNP could more significantly enhance the content of selenocysteine (SeCys) and methylselenocysteine (MeSeCys) in grass carp muscle tissue. In addition, we have demonstrated that SeCys and MeSeCys promote apoptosis of cancer cells (HeLa) through the mitochondrial apoptotic pathway (involving Bax and Bcl-2). Furthermore, as an additive, 0.3 mg/kg SeNP significantly improved the flesh quality of grass carp by reducing crude fat and heavy metal content, as well as increasing the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the ratio of n-3/n-6 polyunsaturated fatty acid (PUFA). In summary, SeNP is the most suitable additive for producing selenium-enriched fish.
PubMed: 38357572
DOI: 10.1016/j.aninu.2023.11.002 -
Molecules (Basel, Switzerland) Dec 2023Selenocysteine selenenic acids (Sec-SeOHs) and selenocysteine selenenyl iodides (Sec-SeIs) have long been recognized as crucial intermediates in the catalytic cycle of...
Selenocysteine selenenic acids (Sec-SeOHs) and selenocysteine selenenyl iodides (Sec-SeIs) have long been recognized as crucial intermediates in the catalytic cycle of glutathione peroxidase (GPx) and iodothyronine deiodinase (Dio), respectively. However, the observation of these reactive species remained elusive until our recent study, where we successfully stabilized Sec-SeOHs and Sec-SeIs using a protective molecular cradle. Here, we report the first demonstration of the chemical transformation from a Sec-SeI to a Sec-SeOH through alkaline hydrolysis. A stable Sec-SeI derived from a selenocysteine methyl ester was synthesized using the protective cradle, and its structure was determined by crystallographic analysis. The alkaline hydrolysis of the Sec-SeI at -50 °C yielded the corresponding Sec-SeOH in an 89% NMR yield, the formation of which was further confirmed by its reaction with dimedone. The facile and nearly quantitative conversion of the Sec-SeI to the Sec-SeOH not only validates the potential involvement of this process in the catalytic mechanism of Dio, but also highlights its utility as a method for producing a Sec-SeOH.
Topics: Selenocysteine; Iodides; Oxidation-Reduction; Hydrolysis; Glutathione Peroxidase
PubMed: 38138461
DOI: 10.3390/molecules28247972 -
The ISME Journal Jun 2024Selenocysteine (Sec) is encoded by the UGA codon that normally functions as a stop signal and is specifically incorporated into selenoproteins via a unique recoding...
Selenocysteine (Sec) is encoded by the UGA codon that normally functions as a stop signal and is specifically incorporated into selenoproteins via a unique recoding mechanism. The translational recoding of UGA as Sec is directed by an unusual RNA structure, the Sec insertion sequence (SECIS) element. Although archaea and eukaryotes adopt a similar Sec encoding machinery, the SECIS elements have no similarities to each other with regard to sequence and structure. We analyzed more than 400 Asgard archaeal genomes to examine the occurrence of both Sec encoding system and selenoproteins in this archaeal superphylum, the closest prokaryotic relatives of eukaryotes. A comprehensive map of Sec utilization trait has been generated, providing the most detailed understanding of the use of this nonstandard amino acid in Asgard archaea so far. By characterizing the selenoproteomes of all organisms, several selenoprotein-rich phyla and species were identified. Most Asgard archaeal selenoprotein genes possess eukaryotic SECIS-like structures with varying degrees of diversity. Moreover, euryarchaeal SECIS elements might originate from Asgard archaeal SECIS elements via lateral gene transfer, indicating a complex and dynamic scenario of the evolution of SECIS element within archaea. Finally, a roadmap for the transition of eukaryotic SECIS elements from archaea was proposed, and selenophosphate synthetase may serve as a potential intermediate for the generation of ancestral eukaryotic SECIS element. Our results offer new insights into a deeper understanding of the evolution of Sec insertion machinery.
PubMed: 38896033
DOI: 10.1093/ismejo/wrae111 -
Biological Trace Element Research Dec 2023Seleno-Yeasts (SY) used as feed additives are known to contain different Selenium (Se) species. Seleno-Yeasts has been shown, on previous analytical methods, to contain...
Seleno-Yeasts (SY) used as feed additives are known to contain different Selenium (Se) species. Seleno-Yeasts has been shown, on previous analytical methods, to contain selenomethionine (SeMet), selenocysteine (SeCys), selenate (Se) and selenite (Se), and various other organic and inorganic Se forms identified but rarely quantified. A new advanced method has allowed elemental Se (Se), an inorganic Se species, to be quantified, thereby obtaining better insight into the proportion of inorganic Se in SY products. The study aimed to quantify the Se in SY products and assess the proportion of inorganic Se in SY. The Se speciation of 13 fresh commercials SY from different suppliers and batches, was assayed for the total Se, inorganic Se species (Se, Se and Se), and organic Se species (SeMet and SeCys). Results on total Se were in line with the expected Se concentrations for all evaluated samples. The proportion of Se present as Se ranged from 3.6% to 51.8%. The quantity of Se in the SY products, added to Se and Se, indicated an average proportion of inorganic Se of 14.2% for the 13 analyzed SY products. The proportion of Se as SeMet ranged from 19.0% to 71.8%, (average of 55.8%), and a large variability in the SeMet content was observed. The SeCys content was also variable, with an average of 3.8%, relative to the total Se. In conclusion, advances in the analytical characterization have revealed that SY products can have a significantly high proportion of inorganic Se, which could affect the bioavailability of Se from SY supplements and explain their variable and lower bio-efficacy than pure SeMet supplements, such as hydroxy-selenomethionine.
Topics: Selenium; Selenomethionine; Dietary Supplements; Selenium Compounds; Yeasts; Selenocysteine
PubMed: 36934195
DOI: 10.1007/s12011-023-03633-z