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Full-Text Articles in Life Sciences
Evidence For Direct Roles Of Two Additional Factors, Secp43 And Soluble Liver Antigen, In The Selenoprotein Synthesis Machinery, Xue-Ming Xu, Heiko Mix, Bradley A. Carlson, Paula J. Grabowski, Vadim N. Gladyshev, Marla J. Berry, Dolph L. Hatfield
Evidence For Direct Roles Of Two Additional Factors, Secp43 And Soluble Liver Antigen, In The Selenoprotein Synthesis Machinery, Xue-Ming Xu, Heiko Mix, Bradley A. Carlson, Paula J. Grabowski, Vadim N. Gladyshev, Marla J. Berry, Dolph L. Hatfield
Vadim Gladyshev Publications
Selenocysteine (Sec) is inserted into selenoproteins co-translationally with the help of various cis- and trans-acting factors. The specific mechanisms of Sec biosynthesis and insertion into protein in eukaryotic cells, however, are not known. Two proteins, SECp43 and the soluble liver antigen (SLA), were previously reported to interact with tRNA [Ser]Sec, but their functions remained elusive. Herein, we report that knockdown of SECp43 in NIH3T3 or TCMK-1 cells using RNA interference technology resulted in a reduction in the level of methylation at the 2’-hydroxylribosyl moiety in the wobble position (Um34) of Sec tRNA [Ser]Sec, and consequently reduced glutathione peroxidase …
Different Catalytic Mechanisms In Mammalian Selenocysteine- And Cysteine-Containing Methionine-R-Sulfoxide Reductases, Hwa-Young Kim, Vadim Gladyshev
Different Catalytic Mechanisms In Mammalian Selenocysteine- And Cysteine-Containing Methionine-R-Sulfoxide Reductases, Hwa-Young Kim, Vadim Gladyshev
Vadim Gladyshev Publications
Selenocysteine (Sec) is found in active sites of several oxidoreductases in which this residue is essential for catalytic activity. However, many selenoproteins have fully functional orthologs, wherein cysteine (Cys) occupies the position of Sec. The reason why some enzymes evolve into selenoproteins if the Cys versions may be sufficient is not understood. Among three mammalian methionine-R-sulfoxide reductases (MsrBs), MsrB1 is a Sec-containing protein, whereas MsrB2 and MsrB3 contain Cys in the active site, making these enzymes an excellent system for addressing the question of why Sec is used in biological systems. In this study, we found that residues, which are …
A Novel Cysteine-Rich Domain Of Sep15 Mediates The Interaction With Udp-Glucose:Glycoprotein Glucosyltransferase, Vyacheslav M. Labunskyy, Andrew D. Ferguson, Dmitri E. Fomenko, Yogarany Chelliah, Dolph L. Hatfield, Vadim N. Gladyshev
A Novel Cysteine-Rich Domain Of Sep15 Mediates The Interaction With Udp-Glucose:Glycoprotein Glucosyltransferase, Vyacheslav M. Labunskyy, Andrew D. Ferguson, Dmitri E. Fomenko, Yogarany Chelliah, Dolph L. Hatfield, Vadim N. Gladyshev
Vadim Gladyshev Publications
Selenium is an essential trace element with potent cancer prevention activity in mammals. The 15-kDa selenoprotein (Sep15) has been implicated in the chemopreventive effect of dietary selenium. Although the precise function of Sep15 remains elusive, Sep15 copurifies with UDP-glucose:glycoprotein glucosyltransferase (GT), an essential regulator of quality control mechanisms within the endoplasmic reticulum. Recent studies identified two GT and two Sep15 homologues in mammals. We characterize interactions between these protein families in this report. Sep15 and GT form a tight 1:1 complex, and these interactions are conserved between mammals and fruit flies. In mammalian cells, Sep15 co-immunoprecipitates with both GT isozymes. …
Crystal Structures Of Oxidized And Reduced Mitochondrial Thioredoxin Reductase Provide Molecular Details Of The Reaction Mechanism, Ekaterina I. Biterova, Anton A. Turanov, Vadim N. Gladyshev, Joseph J. Barycki
Crystal Structures Of Oxidized And Reduced Mitochondrial Thioredoxin Reductase Provide Molecular Details Of The Reaction Mechanism, Ekaterina I. Biterova, Anton A. Turanov, Vadim N. Gladyshev, Joseph J. Barycki
Vadim Gladyshev Publications
Thioredoxin reductase (TrxR) is an essential enzyme required for the efficient maintenance of the cellular redox homeostasis, particularly in cancer cells that are sensitive to reactive oxygen species. In mammals, distinct isozymes function in the cytosol and mitochondria. Through an intricate mechanism, these enzymes transfer reducing equivalents from NADPH to bound FAD and subsequently to an active-site disulfide. In mammalian TrxRs, the dithiol then reduces a mobile C-terminal selenocysteine- containing tetrapeptide of the opposing subunit of the dimer. Once activated, the C-terminal redox center reduces a disulfide bond within thioredoxin. In this report, we present the structural data on a …
Evolution Of Selenium Utilization Traits, Hector Romero, Yan Zhang, Vadim Gladyshev, Gustavo Salinas
Evolution Of Selenium Utilization Traits, Hector Romero, Yan Zhang, Vadim Gladyshev, Gustavo Salinas
Vadim Gladyshev Publications
Background: The essential trace element selenium is used in a wide variety of biological processes. Selenocysteine (Sec), the 21st amino acid, is co-translationally incorporated into a restricted set of proteins. It is encoded by an UGA codon with the help of tRNASec (SelC), Sec-specific elongation factor (SelB) and a cis-acting mRNA structure (SECIS element). In addition, Sec synthase (SelA) and selenophosphate synthetase (SelD) are involved in the biosynthesis of Sec on the tRNASec. Selenium is also found in the form of 2-selenouridine, a modified base present in the wobble position of certain tRNAs, whose synthesis is …
Mammalian Selenoprotein Thioredoxin-Glutathione Reductase, Dan Su, Sergey V. Novoselov, Qi-An Sun, Mohamed E. Moustafa, You Zhou, Richard Oko, Dolph L. Hatfield, Vadim N. Gladyshev
Mammalian Selenoprotein Thioredoxin-Glutathione Reductase, Dan Su, Sergey V. Novoselov, Qi-An Sun, Mohamed E. Moustafa, You Zhou, Richard Oko, Dolph L. Hatfield, Vadim N. Gladyshev
Vadim Gladyshev Publications
Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization …
Pyrrolysine And Selenocysteine Use Dissimilar Decoding Strategies, Yan Zhang, Pavel V. Baranov, John F. Atkins, Vadim N. Gladyshev
Pyrrolysine And Selenocysteine Use Dissimilar Decoding Strategies, Yan Zhang, Pavel V. Baranov, John F. Atkins, Vadim N. Gladyshev
Vadim Gladyshev Publications
Selenocysteine (Sec) and pyrrolysine (Pyl) are known as the 21st and 22nd amino acids in protein. Both are encoded by codons that normally function as stop signals. Sec specification by UGA codons requires the presence of a cis-acting selenocysteine insertion sequence (SECIS) element. Similarly, it is thought that Pyl is inserted by UAG codons with the help of a putative pyrrolysine insertion sequence (PYLIS) element. Herein, we analyzed the occurrence of Pyl-utilizing organisms, Pyl-associated genes, and Pyl-containing proteins. The Pyl trait is restricted to several microbes, and only one organism has both Pyl and Sec. We found that methanogenic …
Selenocysteine Insertion Directed By The 3’-Utr Secis Element In Escherichia Coli, Dan Su, Yehua Li, Vadim Gladyshev
Selenocysteine Insertion Directed By The 3’-Utr Secis Element In Escherichia Coli, Dan Su, Yehua Li, Vadim Gladyshev
Vadim Gladyshev Publications
Co-translational insertion of selenocysteine (Sec) into proteins in response to UGA codons is directed by selenocysteine insertion sequence (SECIS) elements. In known bacterial selenoprotein genes, SECIS elements are located in the coding regions immediately downstream of UGA codons. Here, we report that a distant SECIS element can also function in Sec insertion in bacteria provided that it is spatially close to the UGA codon. We expressed a mammalian phospholipid hydroperoxide glutathione peroxidase in Escherichia coli from a construct in which a natural E.coli SECIS element was located in the 3’-untranslated region (3’-UTR) and adjacent to a sequence complementary to the …
Nematode Selenoproteome: The Use Of The Selenocysteine Insertion System To Decode One Codon In An Animal Genome?, Kalin Taskov, Charles Chapple, Gregory V. Kryukov, Sergi Castenello, Alexei V. Lobanov, Konstantin V. Korotkov, Roderic Guigo, Vadim Gladyshev
Nematode Selenoproteome: The Use Of The Selenocysteine Insertion System To Decode One Codon In An Animal Genome?, Kalin Taskov, Charles Chapple, Gregory V. Kryukov, Sergi Castenello, Alexei V. Lobanov, Konstantin V. Korotkov, Roderic Guigo, Vadim Gladyshev
Vadim Gladyshev Publications
Selenocysteine (Sec) is co-translationally inserted into selenoproteins in response to codon UGA with the help of the selenocysteine insertion sequence (SECIS) element.The number of selenoproteinsinanimals varies, with humans having 25 and mice having 24 selenoproteins. To date, however, only one selenoprotein, thioredoxin reductase, has been detected in Caenorhabditis elegans, and this enzyme contains only one Sec. Here, we characterize the selenoproteomes of C.elegans and Caenorhabditis briggsae with three independent algorithms,one searching for pairs of homologous nematode SECIS elements, another searching for Cys- or Sec-containing homologs of potential nematode selenoprotein genes and the third identifying Sec-containing homologs of annotated nematode …
The Microbial Selenoproteome Of The Sargasso Sea, Yan Zhang, Dmitri E. Fomenko, Vadim Gladyshev
The Microbial Selenoproteome Of The Sargasso Sea, Yan Zhang, Dmitri E. Fomenko, Vadim Gladyshev
Vadim Gladyshev Publications
Background: Selenocysteine (Sec) is a rare amino acid which occurs in proteins in major domains of life. It is encoded by TGA, which also serves as the signal for termination of translation, precluding identification of selenoprotein genes by available annotation tools. Information on full sets of selenoproteins (selenoproteomes) is essential for understanding the biology of selenium. Herein, we characterized the selenoproteome of the largest microbial sequence dataset, the Sargasso Sea environmental genome project. Results: We identified 310 selenoprotein genes that clustered into 25 families, including 101 new selenoprotein genes that belonged to 15 families. Most of these proteins were predicted …
Um34 In Selenocysteine Trna Is Required For The Expression Of Stress-Related Selenoproteins In Mammals, Bradley A. Carlson, Xue-Ming Xu, Vadim N. Gladyshev, Dolph L. Hatfield
Um34 In Selenocysteine Trna Is Required For The Expression Of Stress-Related Selenoproteins In Mammals, Bradley A. Carlson, Xue-Ming Xu, Vadim N. Gladyshev, Dolph L. Hatfield
Vadim Gladyshev Publications
Selenium is an essential micronutrient in the diet of mammals and has many health benefits. Selenium-containing proteins are responsible for most, if not all, of these benefits. This element is incorporated into protein as selenocysteine (Sec), the 21st amino acid in the genetic code. There are two species of Sec tRNA in mammalian cells that differ by a single 2’-O-hydroxymethyl group on the ribosyl moiety at position 34 (Um34). The relationship between this modification and selenoprotein synthesis was examined in mice in which the wild type Sec tRNA gene was replaced with a mutant Sec tRNA transgene incapable of …
Selective Rescue Of Selenoprotein Expression In Mice Lacking A Highly Specialized Methyl Group In Selenocysteine Trna, Bradley A. Carlson, Xue-Ming Xu, Vadim N. Gladyshev, Dolph L. Hatfield
Selective Rescue Of Selenoprotein Expression In Mice Lacking A Highly Specialized Methyl Group In Selenocysteine Trna, Bradley A. Carlson, Xue-Ming Xu, Vadim N. Gladyshev, Dolph L. Hatfield
Vadim Gladyshev Publications
Selenocysteine (Sec) is the 21st amino acid in the genetic code. Its tRNA is variably methylated on the 2’-Ohydroxyl site of the ribosyl moiety at position 34 (Um34). Herein, we identified a role of Um34 in regulating the expression of some, but not all, selenoproteins. A strain of knock-out transgenic mice was generated, wherein the Sec tRNA gene was replaced with either wild type or mutant Sec tRNA transgenes. The mutant transgene yielded a tRNA that lacked two base modifications, N6- isopentenyladenosine at position 37 (i6A37) and Um34. Several selenoproteins, including glutathione peroxidases 1 and 3, …