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

Selenoproteins Regulate Macrophage Invasiveness And Extracellular Matrix-Related Gene Expression, Bradley A. Carlson, Min-Hyuk Yoo, Yasuyo Sano, Aniruddha Sengupta, Jin Young Kim, Robert Irons, Vadim N. Gladyshev, Dolph L. Hatfield, Jin Mo Park Oct 2009

Selenoproteins Regulate Macrophage Invasiveness And Extracellular Matrix-Related Gene Expression, Bradley A. Carlson, Min-Hyuk Yoo, Yasuyo Sano, Aniruddha Sengupta, Jin Young Kim, Robert Irons, Vadim N. Gladyshev, Dolph L. Hatfield, Jin Mo Park

Vadim Gladyshev Publications

Background: Selenium, a micronutrient whose deficiency in diet causes immune dysfunction and inflammatory disorders, is thought to exert its physiological effects mostly in the form of selenium-containing proteins (selenoproteins). Incorporation of selenium into the amino acid selenocysteine (Sec), and subsequently into selenoproteins is mediated by Sec tRNA[Ser]Sec.
Results: To define macrophage-specific selenoprotein functions, we generated mice with the Sec tRNA[Ser]Sec gene specifically deleted in myeloid cells. These mutant mice were devoid of the "selenoproteome" in macrophages, yet exhibited largely normal inflammatory responses. However, selenoprotein deficiency led to aberrant expression of extracellular matrix-related genes, and diminished migration ...


Msrb1 (Methionine-R-Sulfoxide Reductase 1) Knock-Out Mice: Roles Of Msrb1 In Redox Regulation And Identification Of A Novel Selenoprotein Form, Dmitri E. Fomenko, Sergey V. Novoselov, Sathish Kumar Natarajan, Byung Cheon Lee, Ahmet Koc, Bradley A. Carlson, Tae-Hyung Lee, Hwa-Young Kim, Dolph L. Hatfield, Vadim N. Gladyshev Feb 2009

Msrb1 (Methionine-R-Sulfoxide Reductase 1) Knock-Out Mice: Roles Of Msrb1 In Redox Regulation And Identification Of A Novel Selenoprotein Form, Dmitri E. Fomenko, Sergey V. Novoselov, Sathish Kumar Natarajan, Byung Cheon Lee, Ahmet Koc, Bradley A. Carlson, Tae-Hyung Lee, Hwa-Young Kim, Dolph L. Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Protein oxidation has been linked to accelerated aging and is a contributing factor to many diseases. Methionine residues are particularly susceptible to oxidation, but the resulting mixture of methionine R-sulfoxide (Met-RO) and methionine S-sulfoxide (Met-SO) can be repaired by thioredoxin-dependent enzymes MsrB and MsrA, respectively. Here, we describe a knock-out mouse deficient in selenoprotein MsrB1, the main mammalian MsrB located in the cytosol and nucleus. In these mice, in addition to the deletion of 14-kDa MsrB1, a 5-kDa selenoprotein form was specifically removed. Further studies revealed that the 5-kDa protein occurred in both mouse tissues and humanHEK293 cells ...


The Outcome Of Selenium And Vitamin E Cancer Prevention Trial (Select) Reveals The Need For Better Understanding Of Selenium Biology, Dolph Hatfield, Vadim N. Gladyshev Feb 2009

The Outcome Of Selenium And Vitamin E Cancer Prevention Trial (Select) Reveals The Need For Better Understanding Of Selenium Biology, Dolph Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was one of the largest human cancer prevention trials ever undertaken. Designed to examine the role of selenium and vitamin E in preventing prostate cancer (I) as a double-blind study, SELECT administered daily 200 micrograms of selenium in the form of pure L-selenomethionine, 400 IU of synthetic D,L-α-tocopherol (vitamin E), a combination of these two components, or a placebo to four approximately equally divided groups. SELECT enrollment was undertaken between August 22, 2001 and June 24, 2004, and involved 35.533 healthy males from more than 425 participating ...


Genetic Code Supports Targeted Insertion Of Two Amino Acids By One Codon, Anton Turanov, Alexei Lobanov, Dmitri E. Fomenko, Hilary Morrison, Mitchell Sogin, Lawrence Klobutcher, Dolph Hatfield, Vadim N. Gladyshev Jan 2009

Genetic Code Supports Targeted Insertion Of Two Amino Acids By One Codon, Anton Turanov, Alexei Lobanov, Dmitri E. Fomenko, Hilary Morrison, Mitchell Sogin, Lawrence Klobutcher, Dolph Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Strict one-to-one correspondence between codons and amino acids is thought to be an essential feature of the genetic code. However, we report that one codon can code for two different amino acids with the choice of the inserted amino acid determined by a specific 3’ untranslated region structure and location of the dual-function codon within the messenger RNA (mRNA). We found that the codon UGA specifies insertion of selenocysteine and cysteine in the ciliate Euplotes crassus, that the dual use of this codon can occur even within the same gene, and that the structural arrangements of Euplotes mRNA preserve location-dependent ...


The Selenoproteome Of Clostridium Sp. Ohilas: Characterization Of Anaerobic Bacterial Selenoprotein Methionine Sulfoxide Reductase A, Hwa Young, Yan Zhang, Byung Cheon Lee, Jae-Ryong Kim, Vadim N. Gladyshev Jan 2009

The Selenoproteome Of Clostridium Sp. Ohilas: Characterization Of Anaerobic Bacterial Selenoprotein Methionine Sulfoxide Reductase A, Hwa Young, Yan Zhang, Byung Cheon Lee, Jae-Ryong Kim, Vadim N. Gladyshev

Vadim Gladyshev Publications

Selenocysteine (Sec) is incorporated into proteins in response to UGA codons. This residue is frequently found at the catalytic sites of oxidoreductases. In this study, we characterized the selenoproteome of an anaerobic bacterium, Clostridium sp. (also known as Alkaliphilus oremlandii) OhILA, and identified 13 selenoprotein genes, five of which have not been previously described. One of the detected selenoproteins was methionine sulfoxide reductase A (MsrA), an antioxidant enzyme that repairs oxidatively damaged methionines in a stereospecific manner. To date, little is known about MsrA from anaerobes. We characterized this selenoprotein MsrA which had a single Sec residue at the catalytic ...


X-Ray Fluorescence Microscopy Reveals The Role Of Selenium In Spermatogenesis, Sebastian Kehr, Mikalai I. Malinouski, Lydia Finney, Stefan Vogt, Vyacheslav M. Labunskyy, Marina V. Kasaikina, Bradley A. Carlson, You Zhou, Dolph L. Hatfield, Vadim N. Gladyshev Jan 2009

X-Ray Fluorescence Microscopy Reveals The Role Of Selenium In Spermatogenesis, Sebastian Kehr, Mikalai I. Malinouski, Lydia Finney, Stefan Vogt, Vyacheslav M. Labunskyy, Marina V. Kasaikina, Bradley A. Carlson, You Zhou, Dolph L. Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Selenium (Se) is a trace element with important roles in human health. Several selenoproteins have essential functions in development. However, the cellular and tissue distribution of Se remains largely unknown because of the lack of analytical techniques that image this element with sufficient sensitivity and resolution. Herein, we report that X-ray fluorescence microscopy (XFM) can be used to visualize and quantify the tissue, cellular and subcellular topography of Se. We applied this technique to characterize the role of Se in spermatogenesis and identified a dramatic Se enrichment specifically in late spermatids, a pattern that was not seen in any other ...


Comparative Genomic Analyses Of Nickel, Cobalt And Vitamin B12 Utilization, Yan Zhang, Dmitry Rodionov, Mikhail Gelfand, Vadim N. Gladyshev Jan 2009

Comparative Genomic Analyses Of Nickel, Cobalt And Vitamin B12 Utilization, Yan Zhang, Dmitry Rodionov, Mikhail Gelfand, Vadim N. Gladyshev

Vadim Gladyshev Publications

Background: Nickel (Ni) and cobalt (Co) are trace elements required for a variety of biological processes. Ni is directly coordinated by proteins, whereas Co is mainly used as a component of vitamin B12. Although a number of Ni and Co-dependent enzymes have been characterized, systematic evolutionary analyses of utilization of these metals are limited. Results: We carried out comparative genomic analyses to examine occurrence and evolutionary dynamics of the use of Ni and Co at the level of (i) transport systems, and (ii) metalloproteomes. Our data show that both metals are widely used in bacteria and archaea. Cbi/NikMNQO ...


Selenoproteins That Function In Cancer Prevention And Promotion, Dolph L. Hatfield, Min-Hyuk Yoo, Bradley A. Carlson, Vadim N. Gladyshev Jan 2009

Selenoproteins That Function In Cancer Prevention And Promotion, Dolph L. Hatfield, Min-Hyuk Yoo, Bradley A. Carlson, Vadim N. Gladyshev

Vadim Gladyshev Publications

Of the many health benefits attributed to selenium, the one that has received the most attention is its role in cancer prevention. Selenium-containing proteins (selenoproteins) have been shown in recent years to have roles in cancer prevention. However, selenoproteins have diverse functions and their view as antioxidants is oversimplified. Some selenoproteins appear to have a split personality in having roles both in preventing and promoting cancer. The contrasting roles of one selenoprotein, thioredoxin reductase 1, in cancer are discussed in detail, but as also noted, at least one other selenoprotein may also have such a dual function. In addition, we ...


Identification Of A Novel System For Boron Transport: Atr1 Is A Main Boron Exporter In Yeast, Alaattin Kaya, Huseyin C. Karakaya, Dmitri E. Fomenko, Vadim N. Gladyshev, Ahmet Koc Jan 2009

Identification Of A Novel System For Boron Transport: Atr1 Is A Main Boron Exporter In Yeast, Alaattin Kaya, Huseyin C. Karakaya, Dmitri E. Fomenko, Vadim N. Gladyshev, Ahmet Koc

Vadim Gladyshev Publications

Boron is a micronutrient in plants and animals, but its specific roles in cellular processes are not known. To understand boron transport and functions, we screened a yeast genomic DNA library for genes that confer resistance to the element in Saccharomyces cerevisiae. Thirty boron-resistant transformants were isolated, and they all contained the ATR1 (YML116w) gene. Atr1 is a multidrug resistance transport protein belonging to the major facilitator superfamily. C-terminal green fluorescent protein-tagged Atr1 localized to the cell membrane and vacuole, and ATR1 gene expression was upregulated by boron and several stress conditions. We found that atr1Δ mutants were highly ...


Functions And Evolution Of Selenoprotein Methionine Sulfoxide Reductases, Byung Cheon Lee, Alexander Dikiy, Hwa-Young Kim, Vadim N. Gladyshev Jan 2009

Functions And Evolution Of Selenoprotein Methionine Sulfoxide Reductases, Byung Cheon Lee, Alexander Dikiy, Hwa-Young Kim, Vadim N. Gladyshev

Vadim Gladyshev Publications

Methionine sulfoxide reductases (Msrs) are thiol-dependent enzymes which catalyze conversion of methionine sulfoxide to methionine. Three Msr families, MsrA, MsrB, and fRMsr, are known. MsrA and MsrB are responsible for the reduction of methionine-S-sulfoxide and methionine-R-sulfoxide residues in proteins, respectively, whereas fRMsr reduces free methionine-R-sulfoxide. Besides acting on proteins, MsrA can addi¬tionally reduce free methionine-S-sulfoxide. Some MsrAs and MsrBs evolved to utilize catalytic selenocysteine. This includes MsrB1, which is a major MsrB in cytosol and nucleus in mammalian cells. Specialized machinery is used for insertion of selenocysteine into MsrB1 and other seleno¬proteins at in-frame UGA codons. Selenocysteine offers ...


Eukaryotic Selenoproteins And Selenoproteomes, Alexey V. Lobanov, Dolph L. Hatfield, Vadim N. Gladyshev Jan 2009

Eukaryotic Selenoproteins And Selenoproteomes, Alexey V. Lobanov, Dolph L. Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Selenium is an essential trace element for which both beneficial and toxic effects in human health have been described. It is now clear that the importance of having adequate amounts of this micronutrient in the diet is primarily due to the fact that selenium is required for biosynthesis of selenocysteine, the twenty first naturally occurring amino acid in protein. In this review, we provide an overview of eukaryotic selenoproteins and selenoproteomes, which are sets of selenoproteins in these organisms. In eukaryotes, selenoproteins show a mosaic occurrence, with some organisms, such as vertebrates and algae, having dozens of these proteins, while ...


A Structure-Based Approach For Detection Of Thiol Oxidoreductases And Their Catalytic Redox-Active Cysteine Residues, Stefano M. Marino, Vadim N. Gladyshev Jan 2009

A Structure-Based Approach For Detection Of Thiol Oxidoreductases And Their Catalytic Redox-Active Cysteine Residues, Stefano M. Marino, Vadim N. Gladyshev

Vadim Gladyshev Publications

Cysteine (Cys) residues often play critical roles in proteins, for example, in the formation of structural disulfide bonds, metal binding, targeting proteins to the membranes, and various catalytic functions. However, the structural determinants for various Cys functions are not clear. Thiol oxidoreductases, which are enzymes containing catalytic redox-active Cys residues, have been extensively studied, but even for these proteins there is little understanding of what distinguishes their catalytic redox Cys from other Cys functions. Herein, we characterized thiol oxidoreductases at a structural level and developed an algorithm that can recognize these enzymes by (i) analyzing amino acid and secondary structure ...


Overexpression Of Methionine-R-Sulfoxide Reductases Has No Influence On Fruit Fly Aging, Valentina A. Shchedrina, Gerd Vorbrüggen, Byung Cheon Lee, Hwa-Young Kim, Hadise Kabil, Lawrence G. Harshman, Vadim N. Gladyshev Jan 2009

Overexpression Of Methionine-R-Sulfoxide Reductases Has No Influence On Fruit Fly Aging, Valentina A. Shchedrina, Gerd Vorbrüggen, Byung Cheon Lee, Hwa-Young Kim, Hadise Kabil, Lawrence G. Harshman, Vadim N. Gladyshev

Vadim Gladyshev Publications

Methionine sulfoxide reductases (Msrs) are enzymes that repair oxidized methionine residues in proteins. This function implicated Msrs in antiox¬idant defense and the regulation of aging. There are two known Msr types in animals: MsrA specific for the reduction of methionine-S-sulfoxide, and MsrB that catalyzes the reduction of methionine-R-sulfoxide. In a previous study, overexpression of MsrA in the nervous system of Drosophila was found to extend lifespan by 70%. Overexpression of MsrA in yeast also extended lifespan, whereas MsrB overexpression did so only under cal¬orie restriction conditions. The effect of MsrB overexpression on lifespan has not yet been characterized ...


Selenoproteins Mediate T Cell Immunity Through An Antioxidant Mechanism, Rajeev K. Shrimali, Robert D. Irons, Bradley A. Carlson, Yasuyo Sano, Vadim N. Gladyshev, Jin Mo Park, Dolph L. Hatfield Jul 2008

Selenoproteins Mediate T Cell Immunity Through An Antioxidant Mechanism, Rajeev K. Shrimali, Robert D. Irons, Bradley A. Carlson, Yasuyo Sano, Vadim N. Gladyshev, Jin Mo Park, Dolph L. Hatfield

Vadim Gladyshev Publications

Selenium is an essential dietary element with antioxidant roles in immune regulation, but there is little understanding of how this element acts at the molecular level in host defense and inflammatory disease. Selenium is incorporated into the amino acid selenocysteine (Sec), which in turn is inserted into selenoproteins in a manner dependent on Sec tRNA[Ser]Sec. To investigate the molecular mechanism that links selenium to T cell immunity, we generated mice with selenoprotein-less T cells by cell type-specific ablation of the Sec tRNA[Ser]Sec gene (trsp). Herein, we show that these mutant mice exhibit decreased pools of mature ...


Platyhelminth Mitochondrial And Cytosolic Redox Homeostasis Is Controlled By A Single Thioredoxin Glutathione Reductase And Dependent On Selenium And Glutathione, Mariana Bonilla, Ana Denicola, Sergey V. Novoselov, Anton A. Turanov, Anna Protasio, Darwin Izmendi, Vadim N. Gladyshev, Gustavo Salinas Jun 2008

Platyhelminth Mitochondrial And Cytosolic Redox Homeostasis Is Controlled By A Single Thioredoxin Glutathione Reductase And Dependent On Selenium And Glutathione, Mariana Bonilla, Ana Denicola, Sergey V. Novoselov, Anton A. Turanov, Anna Protasio, Darwin Izmendi, Vadim N. Gladyshev, Gustavo Salinas

Vadim Gladyshev Publications

Platyhelminth parasites are a major health problem in developing countries. In contrast to their mammalian hosts, platyhelminth thiol-disulfide redox homeostasis relies on linked thioredoxin-glutathione systems, which are fully dependent on thioredoxin-glutathione reductase (TGR), a promising drug target. TGR is a homodimeric enzyme comprising a glutaredoxin domain and thioredoxin reductase (TR) domains with a C-terminal redox center containing selenocysteine (Sec). In this study, we demonstrate the existence of functional linked thioredoxin-glutathione systems in the cytosolic and mitochondrial compartments of Echinococcus granulosus, the platyhelminth responsible for hydatid disease. The glutathione reductase (GR) activity of TGR exhibited hysteretic behavior regulated by the [GSSG ...


Molybdoproteomes And Evolution Of Molybdenum Utilization, Yan Zhang, Vadim N. Gladyshev Apr 2008

Molybdoproteomes And Evolution Of Molybdenum Utilization, Yan Zhang, Vadim N. Gladyshev

Vadim Gladyshev Publications

The trace element molybdenum (Mo) is utilized in many life forms, where it is a key component of several enzymes involved in nitrogen, sulfur, and carbon metabolism. With the exception of nitrogenase, Mo is bound in proteins to a pterin, thus forming the molybdenum cofactor (Moco) at the catalytic sites of molybdoenzymes. Although a number of molybdoenzymes are well characterized structurally and functionally, evolutionary analyses of Mo utilization are limited. Here, we carried out comparative genomic and phylogenetic analyses to examine occurrence and evolution of Mo utilization in bacteria, archaea, and eukaryotes at the level of (i) Mo transport and ...


Structure And Catalytic Mechanism Of Eukaryotic Selenocysteine Synthase, Oleg M. Ganichkin, Xue-Ming Xu, Bradley A. Carlson, Heiko Mix, Dolph L. Hatfield, Vadim N. Gladyshev, Markus C. Wahl Feb 2008

Structure And Catalytic Mechanism Of Eukaryotic Selenocysteine Synthase, Oleg M. Ganichkin, Xue-Ming Xu, Bradley A. Carlson, Heiko Mix, Dolph L. Hatfield, Vadim N. Gladyshev, Markus C. Wahl

Vadim Gladyshev Publications

In eukaryotes and Archaea, selenocysteine synthase (SecS) converts O-phospho-L-seryl-tRNA[Ser]Sec into selenocysteyltRNA[Ser]Sec using selenophosphate as the selenium donor compound. The molecular mechanisms underlying SecS activity are presently unknown. We have delineated a 450-residue core of mouse SecS, which retained full selenocysteyl-tRNA[Ser]Sec synthesis activity, and determined its crystal structure at 1.65Å resolution. SecS exhibits three domains that place it in the fold type I family of pyridoxal phosphate (PLP)-dependent enzymes. Two SecS monomers interact intimately and together build up two identical active sites around PLP in a Schiff-base linkage with lysine ...


Comparative Analysis Of Selenocysteine Machinery And Selenoproteome Gene Expression In Mouse Brain Identifies Neurons As Key Functional Sites Of Selenium In Mammals, Yan Zhang, You Zhou, Ulrich Schweizer, Nicolai E. Savaskan, Deame Hua, Jonathan Kipnis, Dolph L. Hatfield, Vadim N. Gladyshev Jan 2008

Comparative Analysis Of Selenocysteine Machinery And Selenoproteome Gene Expression In Mouse Brain Identifies Neurons As Key Functional Sites Of Selenium In Mammals, Yan Zhang, You Zhou, Ulrich Schweizer, Nicolai E. Savaskan, Deame Hua, Jonathan Kipnis, Dolph L. Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Although dietary selenium (Se) deficiency results in phenotypes associated with selenoprotein depletion in various organs, the brain is protected from Se loss. To address the basis for the critical role of Se in brain function, we carried out comparative gene expression analyses for the complete selenoproteome and associated biosynthetic factors. Using the Allen Brain Atlas, we evaluated 159 regions of adult mouse brain and provided experimental analyses of selected selenoproteins. All 24 selenoprotein mRNAs were expressed in the mouse brain. Most strikingly, neurons in olfactory bulb, hippocampus, cerebral cortex, and cerebellar cortex were exceptionally rich in selenoprotein gene expression, in ...


Loss Of Housekeeping Selenoprotein Expression In Mouse Liver Modulates Lipoprotein Metabolism, Aniruddha Sengupta, Bradley A. Carlson, Victoria J. Hoffmann, Vadim N. Gladyshev, Dolph L. Hatfield Jan 2008

Loss Of Housekeeping Selenoprotein Expression In Mouse Liver Modulates Lipoprotein Metabolism, Aniruddha Sengupta, Bradley A. Carlson, Victoria J. Hoffmann, Vadim N. Gladyshev, Dolph L. Hatfield

Vadim Gladyshev Publications

Selenium is incorporated into proteins as selenocysteine (Sec), which is dependent on its specific tRNA, designated tRNA [Ser]Sec. Targeted removal of the tRNA [Ser]Sec gene (Trsp) in mouse hepatocytes previously demonstrated the importance of selenoproteins in liver function. Herein, analysis of plasma proteins in this Trsp knockout mouse revealed increases in apolipoprotein E (ApoE) that was accompanied by elevated plasma cholesterol levels. The expression of genes involved in cholesterol biosynthesis, metabolism and transport were also altered in knockout mice. Additionally, in two transgenic Trsp mutant mouse lines (wherein only housekeeping selenoprotein synthesis was restored), the expression of ApoE ...


Comparative Genomic Analyses Of Copper Transporters And Cuproproteomes Reveal Evolutionary Dynamics Of Copper Utilization And Its Link To Oxygen, Perry Ridge, Yan Zhang, Vadim N. Gladyshev Jan 2008

Comparative Genomic Analyses Of Copper Transporters And Cuproproteomes Reveal Evolutionary Dynamics Of Copper Utilization And Its Link To Oxygen, Perry Ridge, Yan Zhang, Vadim N. Gladyshev

Vadim Gladyshev Publications

Copper is an essential trace element in many organisms and is utilized in all domains of life. It is often used as a cofactor of redox proteins, but is also a toxic metal ion. Intracellular copper must be carefully handled to prevent the formation of reactive oxygen species which pose a threat to DNA, lipids, and proteins. In this work, we examined patterns of copper utilization in prokaryotes by analyzing the occurrence of copper transporters and copper-containing proteins. Many organisms, including those that lack copper-dependent proteins, had copper exporters, likely to protect against copper ions that inadvertently enter the cell ...


Reduced Reliance On The Trace Element Selenium During Evolution Of Mammals, Alexey Lobanov, Dolph Hatfield, Vadim N. Gladyshev Jan 2008

Reduced Reliance On The Trace Element Selenium During Evolution Of Mammals, Alexey Lobanov, Dolph Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Background: Selenium (Se) is an essential trace element that occurs in proteins in the form of selenocysteine (Sec). It is transported throughout the body in the form of Sec residues in Selenoprotein P (SelP), a plasma protein of unclear origin recently proposed as an experimental marker of dietary Se status.
Results: Here, we report that the amino-terminal domain of SelP is distantly related to ancestral bacterial thiol oxidoreductases of the thioredoxin superfamily, and that its carboxy-terminal Se transport domain may have originated in early metazoan evolution by de novo accumulation of Sec residues. Reconstruction of evolutionary changes in the Se ...


In Silico Identification Of Genes Involved In Selenium Metabolism: Evidence For A Third Selenium Utilization Trait, Yan Zhang, Anton Turanov, Dolph Hatfield, Vadim N. Gladyshev Jan 2008

In Silico Identification Of Genes Involved In Selenium Metabolism: Evidence For A Third Selenium Utilization Trait, Yan Zhang, Anton Turanov, Dolph Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Background: Selenium (Se) is a trace element that occurs in proteins in the form of selenocysteine (Sec) and in tRNAs in the form of selenouridine (SeU). Selenophosphate synthetase (SelD) is required for both utilization traits. However, previous research also revealed SelDs in two organisms lacking Sec and SeU, suggesting a possible additional use of Se that is dependent on SelD.
Results: In this study, we conducted comparative genomics and phylogenetic analyses to characterize genes involved in Se utilization. Candidate genes identified included SelA/SelB and YbbB that define Sec and SeU pathways, respectively, and NADH oxidoreductase that is predicted to ...


Selenodb 1.0 : A Database Of Selenoprotein Genes, Proteins And Secis Elements, Sergi Castellano, Vadim N. Gladyshev, Roderic Guigo, Marla J. Berry Jan 2008

Selenodb 1.0 : A Database Of Selenoprotein Genes, Proteins And Secis Elements, Sergi Castellano, Vadim N. Gladyshev, Roderic Guigo, Marla J. Berry

Vadim Gladyshev Publications

Selenoproteins are a diverse group of proteins usually misidentified and misannotated in sequence databases. The presence of an in-frame UGA (stop) codon in the coding sequence of selenoprotein genes precludes their identification and correct annotation. The in-frame UGA codons are recoded to cotranslationally incorporate selenocysteine, a rare selenium-containing amino acid. The development of ad hoc experimental and, more recently, computational approaches have allowed the efficient identification and characterization of the selenoproteomes of a growing number of species. Today, dozens of selenoprotein families have been described and more are being discovered in recently sequenced species, but the correct genomic annotation is ...


Functional Characterization Of Alternatively Spliced Human Secisbp2 Transcript Variants, Laura V. Papp, Junning Wang, Derek Kennedy, Didier Boucher, Yan Zhang, Vadim N. Gladyshev, Ravindra N. Singh, Kum Kum Khanna Jan 2008

Functional Characterization Of Alternatively Spliced Human Secisbp2 Transcript Variants, Laura V. Papp, Junning Wang, Derek Kennedy, Didier Boucher, Yan Zhang, Vadim N. Gladyshev, Ravindra N. Singh, Kum Kum Khanna

Vadim Gladyshev Publications

Synthesis of selenoproteins depends on decoding of the UGA stop codon as the amino acid selenocysteine (Sec). This process requires the presence of a Sec insertion sequence element (SECIS) in the 3’-untranslated region of selenoprotein mRNAs and its interaction with the SECIS binding protein 2 (SBP2). In humans, mutations in the SBP2-encoding gene Sec insertion sequence binding protein 2 (SECISBP2) that alter the amino acid sequence or cause splicing defects lead to abnormal thyroid hormone metabolism. Herein, we present the first in silico and in vivo functional characterization of alternative splicing of SECISBP2. We report a complex splicing pattern ...


Selenoproteinless Animals: Selenophosphate Synthetase Sps1 Functions In A Pathway Unrelated To Selenocysteine Biosynthesis, Alexey V. Lobanov, Dolph Hatfield, Vadim N. Gladyshev Jan 2008

Selenoproteinless Animals: Selenophosphate Synthetase Sps1 Functions In A Pathway Unrelated To Selenocysteine Biosynthesis, Alexey V. Lobanov, Dolph Hatfield, Vadim N. Gladyshev

Vadim Gladyshev Publications

Proteins containing the 21st amino acid, selenocysteine (Sec), have been described in all three domains of life, but the composition of selenoproteomes in organisms varies significantly. Here, we report that aquatic arthropods possess many selenoproteins also detected in other animals and unicellular eukaryotes, and that most of these proteins were either lost or replaced with cysteine-containing homologs in insects. As a result of this selective selenoproteome reduction, fruit flies and mosquitoes have three known selenoproteins, and the honeybee, Apis mellifera, a single detected candidate selenoprotein. Moreover, we identified the red flour beetle, Tribolium castaneum, and the silkworm, Bombyx mori, as ...


A Functional Link Between Housekeeping Selenoproteins And Phase Ii Enzymes, Aniruddha Sengupta, Bradley A. Carlson, James A. Weaver, Sergey V. Novoselov, Dmitri E. Fomenko, Vadim N. Gladyshev, Dolph Hatfield Jan 2008

A Functional Link Between Housekeeping Selenoproteins And Phase Ii Enzymes, Aniruddha Sengupta, Bradley A. Carlson, James A. Weaver, Sergey V. Novoselov, Dmitri E. Fomenko, Vadim N. Gladyshev, Dolph Hatfield

Vadim Gladyshev Publications

Sec (selenocysteine) is biosynthesized on its tRNA and incorporated into selenium-containing proteins (selenoproteins) as the 21st amino acid residue. Selenoprotein synthesis is dependent on Sec tRNA and the expression of this class of proteins can be modulated by altering Sec tRNA expression. The gene encoding Sec tRNA (Trsp) is a single-copy gene and its targeted removal in liver demonstrated that selenoproteins are essential for proper function wherein their absence leads to necrosis and hepatocellular degeneration. In the present study, we found that the complete loss of selenoproteins in liver was compensated for by an enhanced expression of several phase II ...


Trends In Selenium Utilization In Marine Microbial World Revealed Through The Analysis Of The Global Ocean Sampling (Gos) Project, Yan Zhang, Vadim N. Gladyshev Jan 2008

Trends In Selenium Utilization In Marine Microbial World Revealed Through The Analysis Of The Global Ocean Sampling (Gos) Project, Yan Zhang, Vadim N. Gladyshev

Vadim Gladyshev Publications

Selenium is an important trace element that occurs in proteins in the form of selenocysteine (Sec) and in tRNAs in the form of selenouridine. Recent large-scale metagenomics projects provide an opportunity for understanding global trends in trace element utilization. Herein, we characterized the selenoproteome of the microbial marine community derived from the Global Ocean Sampling (GOS) expedition. More than 3,600 selenoprotein gene sequences belonging to 58 protein families were detected, including sequences representing 7 newly identified selenoprotein families, such as homologs of ferredoxin– thioredoxin reductase and serine protease. In addition, a new eukaryotic selenoprotein family, thiol reductase GILT, was ...


Solution Structure Of Selenoprotein W And Nmr Analysis Of Its Interaction With 14-3-3 Proteins, Finn L. Aachmann, Dmitri E. Fomenko, Alice Soragni, Vadim N. Gladyshev, Alexander Dikiy Dec 2007

Solution Structure Of Selenoprotein W And Nmr Analysis Of Its Interaction With 14-3-3 Proteins, Finn L. Aachmann, Dmitri E. Fomenko, Alice Soragni, Vadim N. Gladyshev, Alexander Dikiy

Vadim Gladyshev Publications

Selenium is a trace element with significant biomedical potential. It is essential in mammals due to its occurrence in several proteins in the form of selenocysteine (Sec). One of the most abundant mamma¬lian Sec-containing proteins is selenoprotein W (SelW). This protein of unknown function has a broad expression pattern and contains a candidate CXXU (where U represents Sec) redox motif. Here, we re¬port the solution structure of the Sec13 →Cys variant of mouse SelW determined through high resolution NMR spectroscopy. The protein has a thioredoxin-like fold with the CXXU motif located in an exposed loop similarly to ...


Evolutionary Dynamics Of Eukaryotic Selenoproteomes: Large Selenoproteomes May Associate With Aquatic Life And Small With Terrestrial Life, Alexey V. Lobanov, Dmitri E. Fomenko, Yan Zhang, Aniruddha Sengupta, Dolph L. Hatfield, Vadim N. Gladyshev Oct 2007

Evolutionary Dynamics Of Eukaryotic Selenoproteomes: Large Selenoproteomes May Associate With Aquatic Life And Small With Terrestrial Life, Alexey V. Lobanov, Dmitri E. Fomenko, Yan Zhang, Aniruddha Sengupta, Dolph L. Hatfield, Vadim N. Gladyshev

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 selenoprotein patterns were verified ...


The Chlamydomonas Genome Reveals The Evolution Of Key Animal And Plant Functions, Sabeeha S. Merchant, Simon E. Prochnik, Olivier Vallon, Elizabeth H. Harris, Steven J. Karpowicz, George B. Witman, Astrid Terry, Asaf Salamov, Lillian K. Fritz-Laylin, Laurence Maréchal-Drouard, Wallace F. Marshall, Liang-Hu Qu, David R. Nelson, Anton A. Sanderfoot, Martin H. Spalding, Vladimir V. Kapitonov, Qinghu Ren, Patrick Ferris, Erika Lindquist, Harris Shapiro, Susan M. Lucas, Jane Grimwood, Jeremy Schmutz, Chlamydomonas Annotation Team, Vadim N. Gladyshev, Jgi Annotation Team, Igor V. Grigoriev, Daniel S. Rokhsar, Arthur R. Grossman Oct 2007

The Chlamydomonas Genome Reveals The Evolution Of Key Animal And Plant Functions, Sabeeha S. Merchant, Simon E. Prochnik, Olivier Vallon, Elizabeth H. Harris, Steven J. Karpowicz, George B. Witman, Astrid Terry, Asaf Salamov, Lillian K. Fritz-Laylin, Laurence Maréchal-Drouard, Wallace F. Marshall, Liang-Hu Qu, David R. Nelson, Anton A. Sanderfoot, Martin H. Spalding, Vladimir V. Kapitonov, Qinghu Ren, Patrick Ferris, Erika Lindquist, Harris Shapiro, Susan M. Lucas, Jane Grimwood, Jeremy Schmutz, Chlamydomonas Annotation Team, Vadim N. Gladyshev, Jgi Annotation Team, Igor V. Grigoriev, Daniel S. Rokhsar, Arthur R. Grossman

Vadim Gladyshev Publications

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ~120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell ...