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Biochimica Et Biophysica Acta. General... Nov 2018Selenoprotein synthesis requires the reinterpretation of a UGA stop codon as one that encodes selenocysteine (Sec), a process that requires a set of dedicated... (Review)
Review
BACKGROUND
Selenoprotein synthesis requires the reinterpretation of a UGA stop codon as one that encodes selenocysteine (Sec), a process that requires a set of dedicated translation factors. Among the mammalian selenoproteins, Selenoprotein P (SELENOP) is unique as it contains a selenocysteine-rich domain that requires multiple Sec incorporation events.
SCOPE OF REVIEW
In this review we elaborate on new data and current models that provide insight into how SELENOP is made.
MAJOR CONCLUSIONS
SELENOP synthesis requires a specific set of factors and conditions.
GENERAL SIGNIFICANCE
As the key protein required for proper selenium distribution, SELENOP stands out as a lynchpin selenoprotein that is essential for male fertility, proper neurologic function and selenium metabolism.
PubMed: 29656121
DOI: 10.1016/j.bbagen.2018.04.011 -
RNA Biology 2018Posttranslational modification (PTM) is a key mechanism for regulating diverse protein functions, and thus critically affects many essential biological processes.... (Review)
Review
Posttranslational modification (PTM) is a key mechanism for regulating diverse protein functions, and thus critically affects many essential biological processes. Critical for systematic study of the effects of PTMs is the ability to obtain recombinant proteins with defined and homogenous modifications. To this end, various synthetic and chemical biology approaches, including genetic code expansion and protein chemical modification methods, have been developed. These methods have proven effective for generating site-specific authentic modifications or structural mimics, and have demonstrated their value for in vitro and in vivo functional studies of diverse PTMs. This review will discuss recent advances in chemical biology strategies and their application to various PTM studies.
Topics: Acetylation; Chemistry Techniques, Synthetic; Codon, Terminator; Genetic Code; Glycosylation; Humans; Lysine; Methylation; Nitrates; Phosphorylation; Protein Processing, Post-Translational; Proteome; Selenocysteine; Sulfates; Ubiquitination
PubMed: 28901832
DOI: 10.1080/15476286.2017.1360468 -
Current Opinion in Chemical Biology Aug 2023Selenium is connected to three small molecule antioxidant compounds, ascorbate, α-tocopherol, and ergothioneine. Ascorbate and α-tocopherol are true vitamins, while... (Review)
Review
Selenium is connected to three small molecule antioxidant compounds, ascorbate, α-tocopherol, and ergothioneine. Ascorbate and α-tocopherol are true vitamins, while ergothioneine is a "vitamin-like" compound. Here we review how selenium is connected to all three. Selenium and vitamin E work together as a team to prevent lipid peroxidation. Vitamin E quenches lipid hydroperoxyl radicals and the resulting lipid hydroperoxide is then converted to the lipid alcohol by selenocysteine-containing glutathione peroxidase. Ascorbate reduces the resulting α-tocopheroxyl radical in this reaction back to α-tocopherol with concomitant production of the ascorbyl radical. The ascorbyl radical can be reduced back to ascorbate by selenocysteine-containing thioredoxin reductase. Ergothioneine and ascorbate are both water soluble, small molecule reductants that can reduce free radicals and redox-active metals. Thioredoxin reductase can reduce oxidized forms of ergothioneine. While the biological significance of this is not yet realized, this discovery underscores the centrality of selenium to all three antioxidants.
Topics: Ascorbic Acid; Selenium; Ergothioneine; alpha-Tocopherol; Selenocysteine; Thioredoxin-Disulfide Reductase; Vitamin E; Antioxidants; Vitamins; Oxidation-Reduction; Free Radicals; Lipid Peroxides
PubMed: 37236134
DOI: 10.1016/j.cbpa.2023.102328 -
International Journal of Molecular... Mar 2023Dietary selenium (Se) intake within the physiological range is critical to maintain various biological functions, including antioxidant defence, redox homeostasis,... (Review)
Review
Dietary selenium (Se) intake within the physiological range is critical to maintain various biological functions, including antioxidant defence, redox homeostasis, growth, reproduction, immunity, and thyroid hormone production. Chemical forms of dietary Se are diverse, including organic Se (selenomethionine, selenocysteine, and selenium-methyl-selenocysteine) and inorganic Se (selenate and selenite). Previous studies have largely investigated and compared the health impacts of dietary Se on agricultural stock and humans, where dietary Se has shown various benefits, including enhanced growth performance, immune functions, and nutritional quality of meats, with reduced oxidative stress and inflammation, and finally enhanced thyroid health and fertility in humans. The emergence of nanoparticles presents a novel and innovative technology. Notably, Se in the form of nanoparticles (SeNPs) has lower toxicity, higher bioavailability, lower excretion in animals, and is linked to more powerful and superior biological activities (at a comparable Se dose) than traditional chemical forms of dietary Se. As a result, the development of tailored SeNPs for their use in intensive agriculture and as candidate for therapeutic drugs for human pathologies is now being actively explored. This review highlights the biological impacts of SeNPs on growth and reproductive performances, their role in modulating heat and oxidative stress and inflammation and the varying modes of synthesis of SeNPs.
Topics: Animals; Humans; Selenium; Selenocysteine; Antioxidants; Nanoparticles; Inflammation
PubMed: 37047040
DOI: 10.3390/ijms24076068 -
Antioxidants (Basel, Switzerland) Sep 2019The enzyme selenocysteine β-lyase (SCLY) was first isolated in 1982 from pig livers, followed by its identification in bacteria. SCLY works as a homodimer, utilizing... (Review)
Review
The enzyme selenocysteine β-lyase (SCLY) was first isolated in 1982 from pig livers, followed by its identification in bacteria. SCLY works as a homodimer, utilizing pyridoxal 5'-phosphate as a cofactor, and catalyzing the specific decomposition of the amino acid selenocysteine into alanine and selenide. The enzyme is thought to deliver its selenide as a substrate for selenophosphate synthetases, which will ultimately be reutilized in selenoprotein synthesis. SCLY subcellular localization is unresolved, as it has been observed both in the cytosol and in the nucleus depending on the technical approach used. The highest SCLY expression and activity in mammals is found in the liver and kidneys. Disruption of the gene in mice led to obesity, hyperinsulinemia, glucose intolerance, and hepatic steatosis, with SCLY being suggested as a participant in the regulation of energy metabolism in a sex-dependent manner. With the physiological role of SCLY still not fully understood, this review attempts to discuss the available literature regarding SCLY in animals and provides avenues for possible future investigation.
PubMed: 31480609
DOI: 10.3390/antiox8090357 -
Advances in Clinical Chemistry 2018Selenium (Se) is an essential trace element of significant importance in human health. Diet is the major source of Se, and intake of this element depends on its... (Review)
Review
Selenium (Se) is an essential trace element of significant importance in human health. Diet is the major source of Se, and intake of this element depends on its concentration in food sources as well as the amount of those sources consumed. Unfortunately, daily dietary intake of Se in most European countries is generally low, ∼30-40μg/day, compared with the recommended dietary allowance, ∼55 and 70μg/day for adult females and males, respectively. The importance of Se as an essential trace element is linked to its role as selenocysteine in a number of selenoproteins including antioxidant enzymes glutathione peroxidases (GSH-Pxs), thioredoxin reductases (TrxRs), and selenoprotein P (SePP). These enzymes protect tissues against the damaging effect of reactive oxygen species (ROS) and other endogenous products of cellular metabolism implicated in DNA damage and potentially leading to mutagenesis, cell death, and carcinogenesis. Reduced body Se and antioxidant enzyme activity during pregnancy results in oxidative stress within tissues contributing to premature birth, miscarriage, preeclampsia, and intrauterine growth retardation. Because placenta development is highly dependent on oxygen status, uncontrolled ROS formation is likely detrimental. Despite these findings, the role of Se and Se-dependent enzymes in pregnancy remains controversial. The objective of this review is to explore Se status in pregnancy with respect to adverse outcomes. Effects related to decreased antioxidant activity and increased oxidative stress will be highlighted.
Topics: Animals; Female; Glutathione Peroxidase; Humans; Oxidative Stress; Placenta; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Selenium; Selenocysteine; Selenoproteins
PubMed: 30144839
DOI: 10.1016/bs.acc.2018.05.004 -
Antioxidants & Redox Signaling Oct 2015Selenoproteins employ selenium to supplement the chemistry available through the common 20 amino acids. These powerful enzymes are affiliated with redox biology, often... (Review)
Review
SIGNIFICANCE
Selenoproteins employ selenium to supplement the chemistry available through the common 20 amino acids. These powerful enzymes are affiliated with redox biology, often in connection with the detection, management, and signaling of oxidative stress. Among them, membrane-bound selenoproteins play prominent roles in signaling pathways, Ca(2+) regulation, membrane complexes integrity, and biosynthesis of lipophilic molecules.
RECENT ADVANCES
The number of selenoproteins whose physiological roles, protein partners, expression, evolution, and biosynthesis are characterized is steadily increasing, thus offering a more nuanced view of this specialized family. This review focuses on human membrane selenoproteins, particularly the five least characterized ones: selenoproteins I, K, N, S, and T.
CRITICAL ISSUES
Membrane-bound selenoproteins are the least understood, as it is challenging to provide the membrane-like environment required for their biochemical and biophysical characterization. Hence, their studies rely mostly on biological rather than structural and biochemical assays. Another aspect that has not received much attention is the particular role that their membrane association plays in their physiological function.
FUTURE DIRECTIONS
Findings cited in this review show that it is possible to infer the structure and the membrane-binding mode of these lesser-studied selenoproteins and design experiments to examine the role of the rare amino acid selenocysteine.
Topics: Animals; Cell Membrane; Humans; Protein Binding; Selenocysteine; Selenoproteins; Signal Transduction
PubMed: 26168272
DOI: 10.1089/ars.2015.6388 -
Biochimica Et Biophysica Acta. General... Nov 2018The major biological form of selenium is that of the co-translationally inserted amino acid selenocysteine (Sec). In Archaea, the majority of proteins containing Sec,... (Review)
Review
BACKGROUND
The major biological form of selenium is that of the co-translationally inserted amino acid selenocysteine (Sec). In Archaea, the majority of proteins containing Sec, selenoproteins, are involved in methanogenesis. However, the function of this residue is often not known because selenium-independent homologs of the selenoproteins can be employed, sometimes even in one organism.
SCOPE OF REVIEW
This review summarizes current knowledge about the selenoproteins of Archaea, the metabolic pathways where they are involved, and discusses the (potential) function of individual Sec residues. Also, what is known about the "archaeal" way of selenoprotein synthesis, and the regulatory mechanism leading to the replacement of the selenoproteins with selenium-independent homologs, will be presented. Where appropriate, similarities with (and differences to) the respective steps employed in the other two domains, Bacteria and Eukarya, will be emphasized.
MAJOR CONCLUSIONS
Genetic and biochemical studies guided by analysis of genome sequences of Sec-encoding archaea has revealed that the pathway of Sec synthesis in Archaea and Eukarya are principally identical and that Sec insertion in Eukarya probably evolved from an archaeal mechanism employed prior to the separation of the archaeal and eukaryal lines of decent.
GENERAL SIGNIFICANCE
In light of the emerging close phylogenetic relationship of Eukarya and Archaea, archaeal models may be highly valuable tools for unraveling "eukaryotic" principles in molecular and cell biology.
PubMed: 29656122
DOI: 10.1016/j.bbagen.2018.04.008 -
Archives of Biochemistry and Biophysics Dec 2022The contribution of selenium and selenoproteins in prostate cancer etiology remains elusive, potentially due to insufficient information regarding the biochemical... (Review)
Review
The contribution of selenium and selenoproteins in prostate cancer etiology remains elusive, potentially due to insufficient information regarding the biochemical pathways in which they are involved. There are twenty-five human selenocysteine-containing proteins or selenoproteins as well as a smaller class of selenium-containing proteins that do not include selenocysteine, and their cancer-associated aberrations, both genetic and functional, have evoked special interest, although their contribution to the metabolic reprogramming of prostate cancers remains has not been extensively studied. While benign prostate tissue exhibits a glycolytic phenotype, neoplastic events restore the truncated tricarboxylic acid cycle and enhance oxidative phosphorylation. Two selenium-containing proteins, selenium binding protein 1 and selenoprotein F, affect prostate cancer phenotypes by modulating tumor cell metabolic profiles with significant effects on mitochondrial biology, including oxidative phosphorylation and ATP synthesis. One of the pathways affected by both proteins is the activation of adenosine monophosphate kinase and its downstream signaling with concomitant induction of glycolysis. This review focuses on highlighting the role of these two proteins in modulating the bioenergetic profile of prostate cancer and in maintaining the metabolic plasticity of these cells rendering growth advantage and possible therapeutic resistance.
Topics: Humans; Male; Energy Metabolism; Prostatic Neoplasms; Selenium; Selenium-Binding Proteins; Selenocysteine; Selenoproteins
PubMed: 36334799
DOI: 10.1016/j.abb.2022.109451 -
Angewandte Chemie (International Ed. in... Dec 2023Mild strategies for the selective modification of peptides and proteins are in demand for applications in therapeutic peptide and protein discovery, and in the study of...
Mild strategies for the selective modification of peptides and proteins are in demand for applications in therapeutic peptide and protein discovery, and in the study of fundamental biomolecular processes. Herein, we describe the development of an electrochemical selenoetherification (e-SE) platform for the efficient site-selective functionalization of polypeptides. This methodology utilizes the unique reactivity of the 21st amino acid, selenocysteine, to effect formation of valuable bioconjugates through stable selenoether linkages under mild electrochemical conditions. The power of e-SE is highlighted through late-stage C-terminal modification of the FDA-approved cancer drug leuprolide and assembly of a library of anti-HER2 affibody conjugates bearing complex cargoes. Following assembly by e-SE, the utility of functionalized affibodies for in vitro imaging and targeting of HER2 positive breast and lung cancer cell lines is also demonstrated.
Topics: Selenocysteine; Peptides; Proteins; Cell Line; Antineoplastic Agents
PubMed: 37818778
DOI: 10.1002/anie.202313037