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Nutrients May 2015Most human selenium containing proteins contain selenium in the form of the amino acid selenocysteine, which is encoded in the corresponding mRNA as a UGA codon. Only a... (Review)
Review
Most human selenium containing proteins contain selenium in the form of the amino acid selenocysteine, which is encoded in the corresponding mRNA as a UGA codon. Only a few non-selenocysteine containing selenoproteins are present and the nature of the association with selenium is not well understood. This review focuses on two selenocysteine-containing proteins that are members of the glutathione peroxidase family, GPx-1 and GPx-4, and the selenium-associated protein referred to as Selenium Binding Protein 1. Each of these proteins have been described to reside in two or more cellular compartments, and in the case of GPx-1 and SBP1, interact with each other. The enzymatic activity of GPx-1 and GPx-4 have been well described, but it is less clear how their cellular location impacts the health related phenotypes associated with activities, while no catalytic function is assigned to SBP1. The distribution of these proteins is presented as is the possible consequences of that compartmentalization.
Topics: Cell Nucleus; Cytoplasm; Glutathione Peroxidase; Humans; Selenium; Selenium-Binding Proteins; Selenocysteine; Selenoproteins
PubMed: 26007340
DOI: 10.3390/nu7053938 -
Molecules (Basel, Switzerland) Dec 2023Living organisms use selenium mainly in the form of selenocysteine in the active site of oxidoreductases. Here, selenium's unique chemistry is believed to modulate the... (Review)
Review
Living organisms use selenium mainly in the form of selenocysteine in the active site of oxidoreductases. Here, selenium's unique chemistry is believed to modulate the reaction mechanism and enhance the catalytic efficiency of specific enzymes in ways not achievable with a sulfur-containing cysteine. However, despite the fact that selenium/sulfur have different physicochemical properties, several selenoproteins have fully functional cysteine-containing homologues and some organisms do not use selenocysteine at all. In this review, selected selenocysteine-containing proteins will be discussed to showcase both situations: (i) selenium as an obligatory element for the protein's physiological function, and (ii) selenium presenting no clear advantage over sulfur (functional proteins with either selenium or sulfur). Selenium's physiological roles in antioxidant defence (to maintain cellular redox status/hinder oxidative stress), hormone metabolism, DNA synthesis, and repair (maintain genetic stability) will be also highlighted, as well as selenium's role in human health. Formate dehydrogenases, hydrogenases, glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases will be herein featured.
Topics: Humans; Selenium; Cysteine; Selenocysteine; Sulfur; Oxidation-Reduction; Biology
PubMed: 38202704
DOI: 10.3390/molecules29010120 -
Nucleic Acids Research 2006The use of selenocysteine (Sec) as the 21st amino acid in the genetic code has been described in all three major domains of life. However, within eukaryotes,...
The use of selenocysteine (Sec) as the 21st amino acid in the genetic code has been described in all three major domains of life. However, within eukaryotes, selenoproteins are only known in animals and algae. In this study, we characterized selenoproteomes and Sec insertion systems in protozoan Apicomplexa parasites. We found that among these organisms, Plasmodium and Toxoplasma utilized Sec, whereas Cryptosporidium did not. However, Plasmodium had no homologs of known selenoproteins. By searching computationally for evolutionarily conserved selenocysteine insertion sequence (SECIS) elements, which are RNA structures involved in Sec insertion, we identified four unique Plasmodium falciparum selenoprotein genes. These selenoproteins were incorrectly annotated in PlasmoDB, were conserved in other Plasmodia and had no detectable homologs in other species. We provide evidence that two Plasmodium SECIS elements supported Sec insertion into parasite and endogenous selenoproteins when they were expressed in mammalian cells, demonstrating that the Plasmodium SECIS elements are functional and indicating conservation of Sec insertion between Apicomplexa and animals. Dependence of the plasmodial parasites on selenium suggests possible strategies for antimalarial drug development.
Topics: Amino Acid Sequence; Animals; Base Sequence; Evolution, Molecular; Malaria; Mice; Molecular Sequence Data; NIH 3T3 Cells; Plasmodium; Plasmodium falciparum; Proteome; Protozoan Proteins; RNA, Transfer, Amino Acyl; Regulatory Sequences, Ribonucleic Acid; Selenocysteine; Selenoproteins; Sequence Alignment
PubMed: 16428245
DOI: 10.1093/nar/gkj450 -
International Journal of Molecular... Dec 2021Decoding of genetic information into polypeptides occurs during translation, generally following the codon assignment rules of the organism's genetic code. However,... (Review)
Review
Decoding of genetic information into polypeptides occurs during translation, generally following the codon assignment rules of the organism's genetic code. However, recoding signals in certain mRNAs can overwrite the normal rules of translation. An exquisite example of this occurs during translation of selenoprotein mRNAs, wherein UGA codons are reassigned to encode for the 21st proteogenic amino acid, selenocysteine. In this review, we will examine what is known about the mechanisms of UGA recoding and discuss the fate of ribosomes that fail to incorporate selenocysteine.
Topics: Animals; Codon, Terminator; Genetic Code; Humans; Protein Biosynthesis; Ribosomes; Selenocysteine; Selenoproteins
PubMed: 34948001
DOI: 10.3390/ijms222413204 -
Molecular Nutrition & Food Research Sep 2011The reactive aldehyde acrolein is a ubiquitous environmental pollutant and is also generated endogenously. It is a strong electrophile and reacts rapidly with... (Review)
Review
The reactive aldehyde acrolein is a ubiquitous environmental pollutant and is also generated endogenously. It is a strong electrophile and reacts rapidly with nucleophiles including thiolates. This review focuses on the effects of acrolein on thioredoxin reductase (TrxR) and thioredoxin (Trx), which are major regulators of intracellular protein thiol redox balance. Acrolein causes irreversible effects on TrxR and Trx, which are consistent with the formation of covalent adducts to selenocysteine and cysteine residues that are key to their activity. TrxR and Trx are more sensitive than some other redox-sensitive proteins, and their prolonged inhibition could disrupt a number of redox-sensitive functions in cells. Among these effects are the oxidation of peroxiredoxins and the activation of apoptosis signal regulating kinase (ASK1). ASK1 promotes MAP kinase activation, and p38 activation contributes to apoptosis and a number of other acrolein-induced stress responses. Overall, the disruption of the TrxR/Trx system by acrolein could be significant early and prolonged events that affect many aspects of redox-sensitive signaling and oxidant stress.
Topics: Acrolein; Endothelium, Vascular; Enzyme Inhibitors; Humans; MAP Kinase Kinase Kinase 5; Peroxiredoxins; Selenocysteine; Signal Transduction; Sulfhydryl Compounds; Thioredoxin-Disulfide Reductase; Thioredoxins; p38 Mitogen-Activated Protein Kinases
PubMed: 21812108
DOI: 10.1002/mnfr.201100224 -
Cell Proliferation May 2021Organic Selenium (Se) compounds such as L-Se-methylselenocysteine (L-SeMC/SeMC) have been employed as a class of anti-oxidant to protect normal tissues and organs from...
OBJECTIVES
Organic Selenium (Se) compounds such as L-Se-methylselenocysteine (L-SeMC/SeMC) have been employed as a class of anti-oxidant to protect normal tissues and organs from chemotherapy-induced systemic toxicity. However, their comprehensive effects on cancer cell proliferation and tumour progression remain elusive.
MATERIALS AND METHODS
CCK-8 assays were conducted to determine the viabilities of cancer cells after exposure to SeMC, chemotherapeutics or combined treatment. Intracellular reactive oxygen species (ROS) levels and lipid peroxidation levels were assessed via fluorescence staining. The efficacy of free drugs or drug-loaded hydrogel against tumour growth was evaluated in a xenograft mouse model.
RESULTS
Among tested cancer cells and normal cells, the A549 lung adenocarcinoma cells showed higher sensitivity to SeMC exposure. In addition, combined treatments with several types of chemotherapeutics induced synergistic lethality. SeMC promoted lipid peroxidation in A549 cells and thereby increased ROS generation. Significantly, the in vivo efficacy of combination therapy was largely potentiated by hydrogel-mediate drug delivery.
CONCLUSIONS
Our study reveals the selectivity of SeMC in the inhibition of cancer cell proliferation and develops an efficient strategy for local combination therapy.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Carriers; Female; Humans; Hydrogels; Lipid Peroxidation; Lung Neoplasms; Mice; Mice, Nude; Reactive Oxygen Species; Selenocysteine; Xenograft Model Antitumor Assays
PubMed: 33793020
DOI: 10.1111/cpr.13038 -
FEBS Letters Jan 2010Selenocysteine and pyrrolysine, known as the 21st and 22nd amino acids, are directly inserted into growing polypeptides during translation. Selenocysteine is synthesized... (Review)
Review
Selenocysteine and pyrrolysine, known as the 21st and 22nd amino acids, are directly inserted into growing polypeptides during translation. Selenocysteine is synthesized via a tRNA-dependent pathway and decodes UGA (opal) codons. The incorporation of selenocysteine requires the concerted action of specific RNA and protein elements. In contrast, pyrrolysine is ligated directly to tRNA(Pyl) and inserted into proteins in response to UAG (amber) codons without the need for complex re-coding machinery. Here we review the latest updates on the structure and mechanisms of molecules involved in Sec-tRNA(Sec) and Pyl-tRNA(Pyl) formation as well as the distribution of the Pyl-decoding trait.
Topics: Codon, Terminator; Genetic Code; Lysine; RNA, Transfer, Amino Acyl; Selenocysteine; Transfer RNA Aminoacylation
PubMed: 19903474
DOI: 10.1016/j.febslet.2009.11.005 -
PloS One 2022Cyanobacteria are prokaryotic Gram-negative organisms prevalent in nearly all habitats. A detailed proteomics study of Cyanobacteria has not been conducted despite...
Cyanobacteria are prokaryotic Gram-negative organisms prevalent in nearly all habitats. A detailed proteomics study of Cyanobacteria has not been conducted despite extensive study of their genome sequences. Therefore, we conducted a proteome-wide analysis of the Cyanobacteria proteome and found Calothrix desertica as the largest (680331.825 kDa) and Candidatus synechococcus spongiarum as the smallest (42726.77 kDa) proteome of the cyanobacterial kingdom. A Cyanobacterial proteome encodes 312.018 amino acids per protein, with a molecular weight of 182173.1324 kDa per proteome. The isoelectric point (pI) of the Cyanobacterial proteome ranges from 2.13 to 13.32. It was found that the Cyanobacterial proteome encodes a greater number of acidic-pI proteins, and their average pI is 6.437. The proteins with higher pI are likely to contain repetitive amino acids. A virtual 2D map of Cyanobacterial proteome showed a bimodal distribution of molecular weight and pI. Several proteins within the Cyanobacterial proteome were found to encode Selenocysteine (Sec) amino acid, while Pyrrolysine amino acids were not detected. The study can enable us to generate a high-resolution cell map to monitor proteomic dynamics. Through this computational analysis, we can gain a better understanding of the bias in codon usage by analyzing the amino acid composition of the Cyanobacterial proteome.
Topics: Isoelectric Point; Proteome; Proteomics; Selenocysteine; Synechococcus
PubMed: 36190972
DOI: 10.1371/journal.pone.0275148 -
Molekuliarnaia Biologiia 2013Universal genetic code provides the ability to encode only twenty "canonical" amino acids, whereas the twenty first amino acid--selenocysteine (Sec), is encoded by one... (Review)
Review
Universal genetic code provides the ability to encode only twenty "canonical" amino acids, whereas the twenty first amino acid--selenocysteine (Sec), is encoded by one of three well-known stop codon (UGA). In terms of molecular biology, selenocysteine is of exceptional interest, the mechanism of its incorporation into synthesized polypeptide chains is very different from that of the other typical 20 amino acids. This process involves some cis- and trans-active factors, such as the SECIS element (Selenocystein insertion sequence), a structure located in the 3'-untranslated region of eukaryotic mRNA, and in the open reading frame immediately after the UGA-selenocysteine codon in bacteria, which, in turn, leads to differences in the mechanism of selenocysteine incorporation in these domains of life. The trans-factors include Sec-tRNA([Ser]Sec) that has a unique system of biosynthesis, Sec-specific elongation factor EFsec and SBP2--Sec binding protein. Thus, for realization of the selenocysteine incorporation process during translation a large number of additional molecules must be synthesized in the cell, this fact makes the selenocysteine containing proteins rather "expensive" and emphasizes their crucial role in metabolism.
Topics: 3' Untranslated Regions; Base Sequence; Molecular Sequence Data; Peptide Elongation Factor 1; Protein Biosynthesis; RNA, Messenger; RNA, Transfer; RNA-Binding Proteins; Ribosomal Proteins; Selenocysteine
PubMed: 24466745
DOI: 10.7868/s0026898413040137 -
Cell Chemical Biology Apr 2017Selenomabs are engineered monoclonal antibodies with one or more translationally incorporated selenocysteine residues. The unique reactivity of the selenol group of...
Selenomabs are engineered monoclonal antibodies with one or more translationally incorporated selenocysteine residues. The unique reactivity of the selenol group of selenocysteine permits site-specific conjugation of drugs. Compared with other natural and unnatural amino acid and carbohydrate residues that have been used for the generation of site-specific antibody-drug conjugates, selenocysteine is particularly reactive, permitting fast, single-step, and efficient reactions under near physiological conditions. Using a tailored conjugation chemistry, we generated highly stable selenomab-drug conjugates and demonstrated their potency and selectivity in vitro and in vivo. These site-specific antibody-drug conjugates built on a selenocysteine interface revealed broad therapeutic utility in liquid and solid malignancy models.
Topics: Animals; Antibodies, Monoclonal; Antineoplastic Agents; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Female; Fluorescein; Humans; Immunoconjugates; Interleukin Receptor Common gamma Subunit; Mice; Mice, Inbred NOD; Mice, Nude; Mice, SCID; Pharmaceutical Preparations; Protein Stability; Receptor, ErbB-2; Selenocysteine; Syndecan-1; Transplantation, Heterologous
PubMed: 28330604
DOI: 10.1016/j.chembiol.2017.02.012