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Vadim Gladyshev Publications

Articles 31 - 60 of 110

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

New Developments In Selenium Biochemistry: Selenocysteine Biosynthesis In Eukaryotes And Archaea, Xue-Ming Xu, Bradley A. Carlson, Yan Zhang, Heiko Mix, Gregory V. Kryukov, Richard S. Glass, Marla J. Berry, Vadim N. Gladyshev, Dolph L. Hatfield Sep 2007

New Developments In Selenium Biochemistry: Selenocysteine Biosynthesis In Eukaryotes And Archaea, Xue-Ming Xu, Bradley A. Carlson, Yan Zhang, Heiko Mix, Gregory V. Kryukov, Richard S. Glass, Marla J. Berry, Vadim N. Gladyshev, Dolph L. Hatfield

Vadim Gladyshev Publications

We used comparative genomics and experimental analyses to show that (1) eukaryotes and archaea, which possess the selenocysteine (Sec) protein insertion machinery contain an enzyme, O-phosphoseryl-transfer RNA (tRNA) [Ser]Sec kinase (designated PSTK), which phosphorylates seryl-tRNA [Ser]Sec to form O-phosphoseryl-tRNA [Ser]Sec and (2) the Sec synthase (SecS) in mammals is a pyridoxal phosphate-containing protein previously described as the soluble liver antigen (SLA). SecS uses the product of PSTK, Ophosphoseryl- tRNA [Ser]Sec, and selenophosphate as substrates to generate selenocysteyltRNA [Ser]Sec. Sec could be synthesized on tRNA [Ser]Sec from selenide, adenosine triphosphate (ATP), and serine using tRNA [Ser]Sec, seryl-tRNA synthetase, …

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Selective Restoration Of The Selenoprotein Population In A Mouse Hepatocyte Selenoproteinless Background With Different Mutant Selenocysteine Trnas Lacking, Bradley A. Carlson, Mohamed E. Moustafa, Aniruddha Sengupta, Ulrich Schweizer, Rajeev Shrimali, Mahadev Rao, Nianxin Zhong, Shulin Wang, Lionel Feigenbaum, Byeong Jae Lee, Vadim N. Gladyshev, Dolph L. Hatfield Sep 2007

Selective Restoration Of The Selenoprotein Population In A Mouse Hepatocyte Selenoproteinless Background With Different Mutant Selenocysteine Trnas Lacking, Bradley A. Carlson, Mohamed E. Moustafa, Aniruddha Sengupta, Ulrich Schweizer, Rajeev Shrimali, Mahadev Rao, Nianxin Zhong, Shulin Wang, Lionel Feigenbaum, Byeong Jae Lee, Vadim N. Gladyshev, Dolph L. Hatfield

Vadim Gladyshev Publications

Novel mouse models were developed in which the hepatic selenoprotein population was targeted for removal by disrupting the selenocysteine (Sec) tRNA [Ser]Sec gene (trsp) and then selenoprotein expression was restored by introducing wild type or mutant trsp transgenes. The selenoprotein population was partially replaced in liver with mutant transgenes encoding mutations at either position 34 (T34->A34) or 37 (A37->G37) in tRNA [Ser]Sec. The A34 transgene product lacked the highly modified 5-methoxycarbonylmethyl-2’ O-methyluridine and its mutant base A was converted to I34. The G37 transgene product lacked the highly modified N6-isopentenyladenosine. Both mutant tRNAs …

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Identification And Characterization Of A Selenoprotein Family Containing A Diselenide Bond In A Redox Motif, Valentina A. Shchedrina, Sergey V. Novoselov, Mikalai I. Malinouski, Vadim N. Gladyshev Aug 2007

Identification And Characterization Of A Selenoprotein Family Containing A Diselenide Bond In A Redox Motif, Valentina A. Shchedrina, Sergey V. Novoselov, Mikalai I. Malinouski, Vadim N. Gladyshev

Vadim Gladyshev Publications

Selenocysteine (Sec, U) insertion into proteins is directed by translational recoding of specific UGA codons located upstream of a stemloop structure known as Sec insertion sequence (SECIS) element. Selenoproteins with known functions are oxidoreductases containing a single redox-active Sec in their active sites. In this work, we identified a family of selenoproteins, designated SelL, containing two Sec separated by two other residues to form a UxxU motif. SelL proteins show an unusual occurrence, being present in diverse aquatic organisms, including fi sh, invertebrates, and marine bacteria. Both eukaryotic and bacterial SelL genes use single SECIS elements for insertion of two …

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High Content Of Proteins Containing 21st And 22nd Amino Acids, Selenocysteine And Pyrrolysine, In A Symbiotic Deltaproteobacterium Of Gutless Worm Olavius Algarvensis, Yan Zhang, Vadim N. Gladyshev Jul 2007

High Content Of Proteins Containing 21st And 22nd Amino Acids, Selenocysteine And Pyrrolysine, In A Symbiotic Deltaproteobacterium Of Gutless Worm Olavius Algarvensis, Yan Zhang, Vadim N. Gladyshev

Vadim Gladyshev Publications

Selenocysteine (Sec) and pyrrolysine (Pyl) are rare amino acids that are cotranslationally inserted into proteins and known as the 21st and 22nd amino acids in the genetic code. Sec and Pyl are encoded by UGA and UAG codons, respectively, which normally serve as stop signals. Herein, we report on unusually large selenoproteomes and pyrroproteomes in a symbiont metagenomic dataset of a marine gutless worm, Olavius algarvensis. We identified 99 selenoprotein genes that clustered into 30 families, including 17 new selenoprotein genes that belong to six families. In addition, several Pyl-containing proteins were identified in this dataset. Most selenoproteins and …

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Nmr Assignments Of 1H, 13C And 15N Spectra Of Methionine Sulfoxide Reductase B1 From Mus Musculus, Lena S. Sal, Finn L. Aachmann, Hwa-Young Kim, Vadim N. Gladyshev, Alexander Dikiy Jul 2007

Nmr Assignments Of 1H, 13C And 15N Spectra Of Methionine Sulfoxide Reductase B1 From Mus Musculus, Lena S. Sal, Finn L. Aachmann, Hwa-Young Kim, Vadim N. Gladyshev, Alexander Dikiy

Vadim Gladyshev Publications

Isotopically labeled, 15N and 15N/13C forms of recombinant methionine-R-sulfoxide reductase 1 (MsrB1, SelR) from Mus musculus were produced, in which catalytic selenocysteine was replaced with cysteine. We report here the 1H, 15N and 13C NMR assignment of the reduced form of this mammalian protein.

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Crystal Structure Of Formate Dehydrogenase H: Catalysis Involving Mo, Molybdopterin, Selenocysteine, And An Fe4S4 Cluster, Jeffrey C. Boyington, Vadim Gladyshev, Sergei V. Khangulov, Thressa C. Stadtman, Peter D. Sun May 2007

Crystal Structure Of Formate Dehydrogenase H: Catalysis Involving Mo, Molybdopterin, Selenocysteine, And An Fe4S4 Cluster, Jeffrey C. Boyington, Vadim Gladyshev, Sergei V. Khangulov, Thressa C. Stadtman, Peter D. Sun

Vadim Gladyshev Publications

Formate dehydrogenase H from Escherichia coli contains selenocysteine (SeCys), molybdenum, two molybdopterin guanine dinucleotide (MGD) cofactors, and an Fe4S4 cluster at the active site and catalyzes the two-electron oxidation of formate to carbon dioxide. The crystal structures of the oxidized [Mo( VI), Fe4S4(ox)] form of formate dehydrogenase H (with and without bound inhibitor) and the reduced [Mo(IV ), Fe4S4(red)] form have been determined, revealing a four-domain ab structure with the molybdenum directly coordinated to selenium and both MGD cofactors. These structures suggest a reaction mechanism that directly involves SeCys …

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A Highly Efficient Form Of The Selenocysteine Insertion Sequence Element In Protozoan Parasites And Its Use In Mammalian Cells, Sergey V. Novoselov, Alexey V. Lobanov, Deame Hua, Marina V. Kasaikina, Dolph L. Hatfield, Vadim Gladyshev May 2007

A Highly Efficient Form Of The Selenocysteine Insertion Sequence Element In Protozoan Parasites And Its Use In Mammalian Cells, Sergey V. Novoselov, Alexey V. Lobanov, Deame Hua, Marina V. Kasaikina, Dolph L. Hatfield, Vadim Gladyshev

Vadim Gladyshev Publications

Selenoproteins are an elite group of proteins containing a rare amino acid, selenocysteine (Sec), encoded by the codon, UGA. In eukaryotes, incorporation of Sec requires a Sec insertion sequence (SECIS) element, a stem–loop structure located in the 3’-untranslated regions of selenoprotein mRNAs. Here we report identification of a noncanonical form of SECIS element in Toxoplasma gondii and Neospora canine, single-celled apicomplexan parasites of humans and domestic animals. This SECIS has a GGGA sequence in the SBP2-binding site in place of AUGA previously considered invariant. Using a combination of computational and molecular techniques, we show that Toxoplasma and Neospora possess …

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Supporting Information For: A Highly Efficient Form Of The Selenocysteine Insertion Sequence Element In Protozoan Parasites And Its Use In Mammalian Cells, Sergey V. Novoselov, Alexey V. Lobanov, Deame Hua, Marina V. Kasaikina, Dolph L. Hatfield, Vadim Gladyshev Apr 2007

Supporting Information For: A Highly Efficient Form Of The Selenocysteine Insertion Sequence Element In Protozoan Parasites And Its Use In Mammalian Cells, Sergey V. Novoselov, Alexey V. Lobanov, Deame Hua, Marina V. Kasaikina, Dolph L. Hatfield, Vadim Gladyshev

Vadim Gladyshev Publications

Selenoproteins are an elite group of proteins containing a rare amino acid, selenocysteine (Sec), encoded by the codon, UGA. In eukaryotes, incorporation of Sec requires a Sec insertion sequence (SECIS) element, a stem–loop structure located in the 3'-untranslated regions of selenoprotein mRNAs. Here we report identification of a noncanonical form of SECIS element in Toxoplasma gondii and Neospora canine, single-celled apicomplexan parasites of humans and domestic animals. This SECIS has a GGGA sequence in the SBP2-binding site in place of AUGA previously considered invariant. Using a combination of computational and molecular techniques, we show that Toxoplasma and Neospora possess …

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Selenoprotein H Is A Nucleolar Thioredoxin-Like Protein With A Unique Expression Pattern, Sergey V. Novoselov, Gregory V. Kryukov, Xue-Ming Xu, Bradley A. Carlson, Dolph L. Hatfield, Vadim N. Gladyshev Apr 2007

Selenoprotein H Is A Nucleolar Thioredoxin-Like Protein With A Unique Expression Pattern, Sergey V. Novoselov, Gregory V. Kryukov, Xue-Ming Xu, Bradley A. Carlson, Dolph L. Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

The human selenoproteome consists of 25 known selenoproteins, but functions of many of these proteins are not known. Selenoprotein H (SelH) is a recently discovered 14-kDa mammalian protein with no sequence homology to functionally characterized proteins. By sensitive sequence and structure analyses, we identified SelH as a thioredoxin fold-like protein in which a conserved CXXU motif (cysteine separated by two other residues from selenocysteine) corresponds to the CXXC motif in thioredoxins. These data suggest a redox function of SelH. Indeed, a recombinant SelH shows significant glutathione peroxidase activity. In addition, SelH has a conserved RKRK motif …

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Selenophosphate Synthetase 2 Is Essential For Selenoprotein Biosynthesis, Xue-Ming Xu, Bradley A. Carlson, Robert Irons, Heiko Mix, Nianxin Zhong, Vadim Gladyshev, Dolph L. Hatfield Apr 2007

Selenophosphate Synthetase 2 Is Essential For Selenoprotein Biosynthesis, Xue-Ming Xu, Bradley A. Carlson, Robert Irons, Heiko Mix, Nianxin Zhong, Vadim Gladyshev, Dolph L. Hatfield

Vadim Gladyshev Publications

Selenophosphate synthetase (SelD) generates the selenium donor for selenocysteine biosynthesis in eubacteria. One homologue of SelD in eukaryotes is SPS1 (selenophosphate synthetase 1) and a second one, SPS2, was identified as a selenoprotein in mammals. Earlier in vitro studies showed SPS2, but not SPS1, synthesized selenophosphate from selenide, whereas SPS1 may utilize a different substrate. The roles of these enzymes in selenoprotein synthesis in vivo remain unknown. To address their function in vivo, we knocked down SPS2 in NIH3T3 cells using small interfering RNA and found that selenoprotein biosynthesis was severely impaired, whereas knockdown of SPS1 had no effect. …

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Novel Metabolism In Chlamydomonas Through The Lens Of Genomics, Arthur R. Grossman, Martin Croft, Vadim N. Gladyshev, Sebeeha S. Merchant, Matthew C. Posewitz, Simon Prochnik, Martin H. Spalding Apr 2007

Novel Metabolism In Chlamydomonas Through The Lens Of Genomics, Arthur R. Grossman, Martin Croft, Vadim N. Gladyshev, Sebeeha S. Merchant, Matthew C. Posewitz, Simon Prochnik, Martin H. Spalding

Vadim Gladyshev Publications

Chlamydomonas has traditionally been exploited as an organism that is associated with sophisticated physiological, genetic and molecular analyses, all of which have been used to elucidate several biological processes, especially photosynthesis and flagella function and assembly. Recently, the genomics of Chlamydomonas has been combined with other technologies to unveil new aspects of metabolism, including inorganic carbon utilization, anaerobic fermentation, the suite and functions of selenoproteins, and the regulation of vitamin biosynthesis. These initial fi ndings represent the first glimpse through a genomic window onto the highly complex metabolisms that characterize a unicellular, photosynthetic eukaryote that has maintained both plant-like and …

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High-Throughput Identification Of Catalytic Redox-Active Cysteine Residues, Dmitri E. Fomenko, Weibing Xing, Blakely M. Adair, David J. Thomas, Vadim Gladyshev Jan 2007

High-Throughput Identification Of Catalytic Redox-Active Cysteine Residues, Dmitri E. Fomenko, Weibing Xing, Blakely M. Adair, David J. Thomas, Vadim Gladyshev

Vadim Gladyshev Publications

Cysteine (Cys) residues often play critical roles in proteins; however, identification of their specific functions has been limited to case-by-case experimental approaches. We developed a procedure for high-throughput identification of catalytic redox-active Cys in proteins by searching for sporadic selenocysteine-Cys pairs in sequence databases. This method is independent of protein family, structure, and taxon. We used it to selectively detect the majority of known proteins with redoxactive Cys and to make additional predictions, one of which was verified. Rapid accumulation of sequence information from genomic and metagenomic projects should allow detection of many additional oxidoreductase families as well as identification …

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Supporting Online Material For “High-Throughput Identification Of Catalytic Redox-Active Cysteine Residues”, Dmitri E. Fomenko, Weibing Xing, Blakely M. Adair, David J. Thomas, Vadim Gladyshev Jan 2007

Supporting Online Material For “High-Throughput Identification Of Catalytic Redox-Active Cysteine Residues”, Dmitri E. Fomenko, Weibing Xing, Blakely M. Adair, David J. Thomas, Vadim Gladyshev

Vadim Gladyshev Publications

Identification of redox-active Cys by homology to selenoproteins
Identification of Cys/Sec pairs
Statistical analysis of redox-active Cys neighborhoods
AdoMet-dependent methyltransferase
Activity of AS3MT and its Cys-to-Ser mutants

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Targeting Thioredoxin Reductase 1 Reduction In Cancer Cells Inhibits Self-Sufficient Growth And Dna Replication, Min-Hyuk Yoo, Xue-Ming Xu, Bradley A. Carlson, Andrew D. Patterson, Vadim N. Gladyshev, Dolph L. Hatfield Jan 2007

Targeting Thioredoxin Reductase 1 Reduction In Cancer Cells Inhibits Self-Sufficient Growth And Dna Replication, Min-Hyuk Yoo, Xue-Ming Xu, Bradley A. Carlson, Andrew D. Patterson, Vadim N. Gladyshev, Dolph L. Hatfield

Vadim Gladyshev Publications

Thioredoxin reductase 1 (TR1) is a major redox regulator in mammalian cells. As an important antioxidant selenoprotein, TR1 is thought to participate in cancer prevention, but is also known to be over-expressed in many cancer cells. Numerous cancer drugs inhibit TR1, and this protein has been proposed as a target for cancer therapy. We previously reported that reduction of TR1 levels in cancer cells reversed many malignant characteristics suggesting that deficiency in TR1 function is antitumorigenic. The molecular basis for TR1’s role in cancer development, however, is not understood. Herein, we found that, among selenoproteins, TR1 is uniquely overexpressed in …

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Biosynthesis Of Selenocysteine On Its Trna In Eukaryotes, Xue-Ming Xu, Bradley A. Carlson, Heiko Mix, Yan Zhang, Kazima Saira, Richard S. Glass, Marla J. Berry, Vadim Gladyshev, Dolph L. Hatfield Jan 2007

Biosynthesis Of Selenocysteine On Its Trna In Eukaryotes, Xue-Ming Xu, Bradley A. Carlson, Heiko Mix, Yan Zhang, Kazima Saira, Richard S. Glass, Marla J. Berry, Vadim Gladyshev, Dolph L. Hatfield

Vadim Gladyshev Publications

Selenocysteine (Sec) is cotranslationally inserted into protein in response to UGA codons and is the 21st amino acid in the genetic code. However, the means by which Sec is synthesized in eukaryotes is not known. Herein, comparative genomics and experimental analyses revealed that the mammalian Sec synthase (SecS) is the previously identified pyridoxal phosphate-containing protein known as the soluble liver antigen. SecS required selenophosphate and Ophosphoseryl- tRNA [Ser]Sec as substrates to generate selenocysteyl-tRNA [Ser]Sec. Moreover, it was found that Sec was synthesized on the tRNA scaffold from selenide, ATP, and serine using tRNA [Ser]Sec, seryl-tRNA synthetase, Ophosphoseryl- tRNA …

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The Sep15 Protein Family: Roles In Disulfide Bond Formation And Quality Control In The Endoplasmic Reticulum, Vyacheslav M. Labunskyy, Dolph L. Hatfield, Vadim N. Gladyshev Jan 2007

The Sep15 Protein Family: Roles In Disulfide Bond Formation And Quality Control In The Endoplasmic Reticulum, Vyacheslav M. Labunskyy, Dolph L. Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Disulfide bonds play an important role in the structure and function of membrane and secretory proteins. The formation of disulfide bonds in the endoplasmic reticulum (ER) of eukaryotic cells is catalyzed by a complex network of thiol-disulfide oxidoreductases. Whereas a number of ER-resident oxidoreductases have been identified, the function of only a few of them is firmly established. Recently, a selenocysteine-containing oxidoreductase, Sep15, has been implicated in disulfide bond assisted protein folding, and a role in quality control for this selenoprotein has been proposed. This review summarizes up-to-date information on the Sep15 family proteins and highlights new insights into their …

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Evolutionary Dynamics Of Eukaryotic Selenoproteomes: Large Selenoproteomes May Associate With Aquatic Life And Small With Terrestrial Life, Alexei Lobanov, Dmitri E. Fomenko, Yan Zhang, Aniruddha Sengupta Jan 2007

Evolutionary Dynamics Of Eukaryotic Selenoproteomes: Large Selenoproteomes May Associate With Aquatic Life And Small With Terrestrial Life, Alexei Lobanov, Dmitri E. Fomenko, Yan Zhang, Aniruddha Sengupta

Vadim Gladyshev Publications

Background: Selenocysteine (Sec) is a selenium-containing amino acid that is co-translationally inserted into nascent polypeptides by recoding UGA codons. Selenoproteins occur in both eukaryotes and prokaryotes, but the selenoprotein content of organisms (selenoproteome) is highly variable and some organisms do not utilize Sec at all.

Results: We analyzed the selenoproteomes of several model eukaryotes and detected 26 and 29 selenoprotein genes in the green algae Ostreococcus tauri and Ostreococcus lucimarinus, respectively, five in the social amoebae Dictyostelium discoideum, three in the fly Drosophila pseudoobscura, and 16 in the diatom Thalassiosira pseudonana, including several new selenoproteins. Distinct …

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Secis Elements In The Coding Regions Of Selenoprotein Transcripts Are Functional In Higher Eukaryotes, Heiko Mix, Alexey V. Lobanov, Vadim Gladyshev Dec 2006

Secis Elements In The Coding Regions Of Selenoprotein Transcripts Are Functional In Higher Eukaryotes, Heiko Mix, Alexey V. Lobanov, Vadim Gladyshev

Vadim Gladyshev Publications

Expression of selenocysteine (Sec)-containing proteins requires the presence of a cis-acting mRNA structure, called selenocysteine insertion sequence (SECIS) element. In bacteria, this structure is located in the coding region immediately downstream of the Sec-encoding UGA codon, whereas in eukaryotes a completely different SECIS element has evolved in the 3’-untranslated region. Here, we report that SECIS elements in the coding regions of selenoprotein mRNAs support Sec insertion in higher eukaryotes. Comprehensive computational analysis of all available viral genomes revealed a SECIS element within the ORF of a naturally occurring selenoprotein homolog of glutathione peroxidase 4 in fowlpox virus. The fowlpox …

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Dynamic Evolution Of Selenocysteine Utilization In Bacteria: A Balance Between Selenoprotein Loss And Evolution Of Selenocysteine From Redox Active Cysteine Residues, Yan Zhang, Hector Romero, Gustavo Salinas, Vadim Gladyshev Oct 2006

Dynamic Evolution Of Selenocysteine Utilization In Bacteria: A Balance Between Selenoprotein Loss And Evolution Of Selenocysteine From Redox Active Cysteine Residues, Yan Zhang, Hector Romero, Gustavo Salinas, Vadim Gladyshev

Vadim Gladyshev Publications

Background: Selenocysteine (Sec) is co-translationally inserted into protein in response to UGA codons. It occurs in oxidoreductase active sites and often is catalytically superior to cysteine (Cys). However, Sec is used very selectively in proteins and organisms. The wide distribution of Sec and its restricted use have not been explained.
Results: We conducted comparative genomics and phylogenetic analyses to examine dynamics of Sec decoding in bacteria at both selenium utilization trait and selenoproteome levels. These searches revealed that 21.5% of sequenced bacteria utilize Sec, their selenoproteomes have 1 to 31 selenoproteins, and selenoprotein-rich organisms are mostly Deltaproteobacteria or Firmicutes/ Clostridia …

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Selenium Metabolism In Trypanosoma: Characterization Of Selenoproteomes And Identification Of A Kinetoplastida-Specific Selenoprotein, Alexey V. Lobanov, Stephan Gromer, Gustavo Salinas, Vadim Gladyshev Aug 2006

Selenium Metabolism In Trypanosoma: Characterization Of Selenoproteomes And Identification Of A Kinetoplastida-Specific Selenoprotein, Alexey V. Lobanov, Stephan Gromer, Gustavo Salinas, Vadim Gladyshev

Vadim Gladyshev Publications

Proteins containing the 21st amino acid selenocysteine (Sec) are present in the three domains of life. However, within lower eukaryotes, particularly parasitic protists, the dependence on the trace element selenium is variable as many organisms lost the ability to utilize Sec. Herein, we analyzed the genomes of Trypanosoma and Leishmania for the presence of genes coding for Sec-containing proteins. The selenoproteomes of these flagellated protozoa have three selenoproteins, including distant homologs of mammalian SelK and SelT, and a novel multidomain selenoprotein designated SelTryp. In SelK and SelTryp, Sec is near the C-terminus, and in all three selenoproteins, it is within …

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Characterization Of Alternative Cytosolic Forms And Cellular Targets Of Mouse Mitochondrial Thioredoxin Reductase, Anton A. Turanov, Dan Su, Vadim N. Gladyshev Aug 2006

Characterization Of Alternative Cytosolic Forms And Cellular Targets Of Mouse Mitochondrial Thioredoxin Reductase, Anton A. Turanov, Dan Su, Vadim N. Gladyshev

Vadim Gladyshev Publications

Thioredoxin reductase (TR) and thioredoxin (Trx) define a major cellular redox system that maintains cysteine residues in numerous proteins in the reduced state. Both cytosolic (TR1 and Trx1) and mitochondrial (TR3 and Trx2) enzymes are essential in mammals, but the function of the mitochondrial system is less understood. In this study, we characterized subcellular localization of three TR3 forms that are generated by alternative first exon splicing and that differ in their N-terminal sequences. Only one of these forms resides in mitochondria, whereas the two other isoforms are cytosolic. Consistent with this finding, TR3 did not have catalytic preferences for …

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Supplementary Material For: Secis Elements In The Coding Regions Of Selenoprotein Transcripts Are Functional In Higher Eukaryotes, Heiko Mix, Alexey V. Lobanov, Vadim Gladyshev Aug 2006

Supplementary Material For: Secis Elements In The Coding Regions Of Selenoprotein Transcripts Are Functional In Higher Eukaryotes, Heiko Mix, Alexey V. Lobanov, Vadim Gladyshev

Vadim Gladyshev Publications

Figure S1. Nucleotide sequence alignment of GPx4 sequences.
For: M. musculus, H. sapiens, G. gallus, A. thaliana, Fowlpox virus, and Canarypox virus

Figure S2. Alignment of GPx4 SECIS elements.
For: H. sapiens, M. musculus, G. gallus, Fowlpox, Canarypox, and MCV

Supplementary Table S1. Viral genome sequences used in a computational analysis
From Abelson murine leukemia virus through Zygosaccharomyces bailii virus Z

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Is There A Twenty Third Amino Acid In The Genetic Code?, Alexey V. Lobanov, Gregory V. Kryukov, Dolph L. Hatfield, Vadim Gladyshev Jul 2006

Is There A Twenty Third Amino Acid In The Genetic Code?, Alexey V. Lobanov, Gregory V. Kryukov, Dolph L. Hatfield, Vadim Gladyshev

Vadim Gladyshev Publications

The universal genetic code includes 20 common amino acids. In addition, selenocysteine (Sec) and pyrrolysine (Pyl), known as the twenty first and twenty second amino acids, are encoded by UGA and UAG, respectively, which are the codons that usually function as stop signals. The discovery of Sec and Pyl suggested that the genetic code could be further expanded by reprogramming stop codons. To search for the putative twenty third amino acid, we employed various tRNA identification programs that scanned 16 archaeal and 130 bacterial genomes for tRNAs with anticodons corresponding to the three stop signals. Our data suggest that the …

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"Preface" To Selenium: Its Molecular Biology And Role In Human Health, Second Edition, Dolph L. Hatfield, Marla J. Berry, Vadim N. Gladyshev Jun 2006

"Preface" To Selenium: Its Molecular Biology And Role In Human Health, Second Edition, Dolph L. Hatfield, Marla J. Berry, Vadim N. Gladyshev

Vadim Gladyshev Publications

The purpose of the new edition book is to inform the reader of many new discoveries and to examine our present knowledge of the molecular biology of selenium, its incorporation into proteins as selenocysteine and the role that this element and selenium-containing proteins (selenoproteins) play in health. The book's emphasis is on our understanding of selenium metabolism in mammals and the role of this element in human health. The book begins with a brief history of selenium and how its face has changed through the years fiom one of a toxin and possible carcinogen to one of an essential micronutrient …

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Selenoproteins And Selenoproteomes, Vadim N. Gladyshev Jun 2006

Selenoproteins And Selenoproteomes, Vadim N. Gladyshev

Vadim Gladyshev Publications

In the past several years, progress in genome sequencing and development of specialized bioinformatics tools allowed efficient identification of selenocysteine-containing proteins encoded in completely sequenced genomes. Information is currently available on selenoproteomes from a variety of organisms, including humans, which contain 25 known selenoprotein genes. This review provides basic information about mammalian selenoproteins and other known selenoprotein families. Analysis of full sets of selenoproteins in organisms provides exciting avenues for examining selenoprotein evolution and dependence of organisms on the trace element selenium and allows linking selenoproteins with specific biological and biomedical effects of dietary selenium.

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Mouse Models For Assessing The Role Of Selenoproteins In Health And Development, Bradley A. Carlson, Xue-Ming Xu, Rajeev Shrimali, Aniruddha Sengupta, Min-Hyuk Yoo, Nianxin Zhong, Dolph L. Hatfield, Robert Irons, Cindy D. Davis, Byeong Jae Lee, Sergey V. Novoselov, Vadim N. Gladyshev Jun 2006

Mouse Models For Assessing The Role Of Selenoproteins In Health And Development, Bradley A. Carlson, Xue-Ming Xu, Rajeev Shrimali, Aniruddha Sengupta, Min-Hyuk Yoo, Nianxin Zhong, Dolph L. Hatfield, Robert Irons, Cindy D. Davis, Byeong Jae Lee, Sergey V. Novoselov, Vadim N. Gladyshev

Vadim Gladyshev Publications

Mouse models have been generated to assess the roles of selenoproteins involved with housekeeping tasks and/or stress-related phenomena in development and health. Each mouse model has taken advantage of the fact that the synthesis of all selenoproteins is dependent on the expression of two selenocysteine (Sec) tRNA[Ser]Sec isoforms that differ fiom each other by a single methyl group on the ribosyl moiety at position 34. The endogenous (Sec) tRNA[Ser]Sec population was selectively altered by generating mouse models involving 1) transgenic animals carrying mutant or wild type (Sec) tRNA[Ser]Sec transgenes, 2) conditional knockout animals carrying a floxed (Sec) tRNA[Ser]Sec gene that …

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Selenium And Methionine Sulfoxide Reduction, Hwa-Young Kim, Vadim N. Gladyshev Jun 2006

Selenium And Methionine Sulfoxide Reduction, Hwa-Young Kim, Vadim N. Gladyshev

Vadim Gladyshev Publications

Methionine residues in proteins can be readily oxidized to a diastereomeric mixture of methionine sulfoxides by reactive oxygen species. In most organisms, methionine sulfoxides are reversibly and stereospecifically reduced back to methionine by two distinct classes of repair enzymes, methionine-S-sulfoxide reductase (MsrA) and methionine-R-sulfoxide reductase (MsrB). Methionine sulfoxide reduction is thought to be an essential pathway that protects cells from oxidative stress and regulates protein function. This pathway is also implicated in delaying the aging process in organisms from yeast to mammals. The first selenoprotein identified using bioinformatics methods, SelR (also known as SelX or MsrB1), was recently found to …

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Evolution Of Selenocysteine Decoding And The Key Role Of Selenophosphate Synthetase In The Pathway Of Selenium Utilization, Gustavo Salinas, Héctor Romero, Xue-Ming Xu, Bradley A. Carlson, Dolph L. Hatfield, Vadim N. Gladyshev Jun 2006

Evolution Of Selenocysteine Decoding And The Key Role Of Selenophosphate Synthetase In The Pathway Of Selenium Utilization, Gustavo Salinas, Héctor Romero, Xue-Ming Xu, Bradley A. Carlson, Dolph L. Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

The complete sequencing of genomes and the development of in silico methods for identification of genes encoding selenocysteine (Sec)-containing proteins have greatly contributed to shape our view on the evolution of selenium utilization in nature. Current evidence is consistent with the idea that Sec decoding is a late addition to the genetic code and it evolved once, before the separation of archaeal, bacterial and eukaryal domains. Many organisms have lost the Sec decoding trait, but recent evidence has shown that the loss is not irreversible. The distribution of organisms that use UGA as a Sec codon suggests that Sec decoding …

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Selenoproteins In Parasites, Gustavo Salinas, Alexei V. Lobanov, Vadim N. Gladyshev Jun 2006

Selenoproteins In Parasites, Gustavo Salinas, Alexei V. Lobanov, Vadim N. Gladyshev

Vadim Gladyshev Publications

Parasites, which cause an enormous burden in the population of the third world, are a diverse group of organisms, many of which are sensitive to oxidative stress imposed by their hosts. In recent years, several selenoprotein families, some with antioxidant properties, have been described and characterized in metazoan parasites. Glutathione peroxidase and thioredoxin glutathione reductase (TGR) appear to be essential selenoproteins in flatworms (phylum Platyhelminthes). TGR is the single enzyme that provides reducing equivalents to both thioredoxin and glutathione pathways, in contrast to hosts, which evolve parallel pathways. In roundworms (phylum Nematoda), selenoproteins have recently been described, revealing …

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The 15-Kda Selenoprotein (Sep15): Functional Analysis And Role In Cancer, Vyacheslav M. Labunskyy, Vadim N. Gladyshev, Dolph L. Hatfield Jun 2006

The 15-Kda Selenoprotein (Sep15): Functional Analysis And Role In Cancer, Vyacheslav M. Labunskyy, Vadim N. Gladyshev, Dolph L. Hatfield

Vadim Gladyshev Publications

The 15-kDa selenoprotein (Sep15) was identified several years ago as a protein of unknown function. In recent years, several lines of evidence implicated Sepl5 in the effect of dietary selenium in cancer prevention. These lines of evidence include: 1) protein expression patterns in normal and malignant cells; 2) identification of polymorphic sites that regulate Sep15 levels and differentially respond to selenium supplementation; 3) location of the Sep15 gene in the human genome; and 4) correlation between Sep15 haplotype and susceptibility to cancer. Functional analyses revealed a specific interaction between Sep15 and a protein folding sensor in the endoplasmic reticulum of …

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