Vadim N. Gladyshev

Selenoproteins regulate macrophage invasiveness and extracellular matrix-related gene expression (2009)

Carlson, Bradley A, Yoo, Min-Hyuk, Sano, Yasuyo, Sengupta, Aniruddha, Kim, Jin, Irons, Robert, ...

Abstract 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...

MsrB1 (Methionine-R-sulfoxide Reductase 1) Knock-out Mice: Roles of MsrB1 in Redox Regulation and Identification of a Novel Selenoprotein Form (2009)

Fomenko, Dmitri E., Novoselov, Sergey V., Natarajan, Sathish Kumar, Lee, Byung Cheon, Koc, Ahmet, Carlson, Bradley A., ...

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...

Comparative genomic analyses of nickel, cobalt and vitamin B12 utilization (2009)

Zhang, Yan, Rodionov, Dmitry A, Gelfand, Mikhail S, Gladyshev, Vadim N

Abstract 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...

The Outcome of Selenium and Vitamin E Cancer Prevention Trial (SELECT) Reveals the Need for Better Understanding of Selenium Biology (2009)

Hatfield, Dolph, Gladyshev, Vadim N.

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...

Genetic Code Supports Targeted Insertion of Two Amino Acids by One Codon (2009)

Turanov, Anton, Lobanov, Alexei, Fomenko, Dmitri E., Morrison, Hilary, Sogin, Mitchell, Klobutcher, Lawrence, ...

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...

The selenoproteome of Clostridium sp. OhILAs: Characterization of anaerobic bacterial selenoprotein methionine sulfoxide reductase A (2009)

Young, Hwa, Zhang, Yan, Cheon Lee, Byung, Kim, Jae-Ryong, Gladyshev, Vadim N.

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...

X-ray Fluorescence Microscopy Reveals the Role of Selenium in Spermatogenesis (2009)

Kehr, Sebastian, Malinouski, Mikalai I., Finney, Lydia, Vogt, Stefan, Labunskyy, Vyacheslav M., Kasaikina, Marina V., ...

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...

Comparative Genomic Analyses of Nickel, Cobalt and Vitamin B12 Utilization (2009)

Zhang, Yan, Rodionov, Dmitry, Gelfand, Mikhail, Gladyshev, Vadim N.

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...

Eukaryotic Selenoproteins and Selenoproteomes (2009)

Lobanov, Alexey V., Hatfield, Dolph L., Gladyshev, Vadim N.

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...

Identification of a Novel System for Boron Transport: Atr1 Is a Main Boron Exporter in Yeast (2009)

Kaya, Alaattin, Karakaya, Huseyin C., Fomenko, Dmitri E., Gladyshev, Vadim N., Koc, Ahmet

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...

A Structure-Based Approach for Detection of Thiol Oxidoreductases and Their Catalytic Redox-Active Cysteine Residues (2009)

Marino, Stefano M., Gladyshev, Vadim N.

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...

Selenoproteins that Function in Cancer Prevention and Promotion (2009)

Hatfield, Dolph L., Yoo, Min-Hyuk, Carlson, Bradley A., Gladyshev, Vadim N.

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...

Functions and Evolution of Selenoprotein Methionine Sulfoxide Reductases (2009)

Cheon Lee, Byung, Dikiy, Alexander, Kim, Hwa-Young, Gladyshev, Vadim N.

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...

Overexpression of Methionine-R-Sulfoxide Reductases has No iInfluence on Fruit Fly Aging (2009)

Shchedrina, Valentina A., Vorbrüggen, Gerd, Lee, Byung Cheon, Kim, Hwa-Young, Kabil, Hadise, Harshman, Lawrence G., ...

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...

Mouse Models Targeting Selenocysteine tRNA Expression for Elucidating the Role of Selenoproteins in Health and Development (2009)

Bradley A. Carlson, Min-Hyuk Yoo, Petra A. Tsuji, Vadim N. Gladyshev, Dolph L. Hatfield

Selenium (Se) deficiency has been known for many years to be associated with disease, impaired growth and a variety of other metabolic disorders in mammals. Only recently has the major role that...

Selenoproteins Mediate T Cell Immunity through an Antioxidant Mechanism (2008)

Shrimali, Rajeev K., Irons, Robert D., Carlson, Bradley A., Sano, Yasuyo, Gladyshev, Vadim N., Park, Jin Mo, ...

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...

Platyhelminth Mitochondrial and Cytosolic Redox Homeostasis Is Controlled by a Single Thioredoxin Glutathione Reductase and Dependent on Selenium and Glutathione (2008)

Bonilla, Mariana, Denicola, Ana, Novoselov, Sergey V., Turanov, Anton A., Protasio, Anna, Izmendi, Darwin, ...

Platyhelminth parasites are a major health problem in developing countries. In contrast to their mammalian hosts, platyhelminth thiol-disulfide redox homeostasis relies on linked...

In silicoidentification of genes involved in selenium metabolism: evidence for a third selenium utilization trait (2008)

Zhang, Yan, Turanov, Anton A, Hatfield, Dolph L, Gladyshev, Vadim N

Abstract 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...

Molybdoproteomes and evolution of molybdenum utilization (2008)

Zhang, Yan, Gladyshev, Vadim N.

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...

A Study in Modeling Low-Conservation Protein (2008)

Chang Wang, Student Member, Stephen D. Scott, Jun Zhang, Qingping Tao, Dmitri E. Fomenko, ...

We present several algorithms for identification of new proteins in superfamilies with low primary sequence conservation. The low conservation of primary sequence in protein superfamilies such as...

Reduced reliance on the trace element selenium during evolution of mammals (2008)

Lobanov, Alexey V, Hatfield, Dolph L, Gladyshev, Vadim N

Abstract 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...

Structure and Catalytic Mechanism of Eukaryotic Selenocysteine Synthase (2008)

Ganichkin, Oleg M., Xu, Xue-Ming, Carlson, Bradley A., Mix, Heiko, Hatfield, Dolph L., Gladyshev, Vadim N., ...

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...

Comparative Analysis of Selenocysteine Machinery and Selenoproteome Gene Expression in Mouse Brain Identifies Neurons as Key Functional Sites of Selenium in Mammals (2008)

Zhang, Yan, Zhou, You, Schweizer, Ulrich, Savaskan, Nicolai E., Hua, Deame, Kipnis, Jonathan, ...

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...

Loss of housekeeping selenoprotein expression in mouse liver modulates lipoprotein metabolism (2008)

Sengupta, Aniruddha, Carlson, Bradley A., Hoffmann, Victoria J., Gladyshev, Vadim N., Hatfield, Dolph L.

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...

Comparative Genomic Analyses of Copper Transporters and Cuproproteomes Reveal Evolutionary Dynamics of Copper Utilization and Its Link to Oxygen (2008)

Ridge, Perry, Zhang, Yan, Gladyshev, Vadim N.

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...

In silico Identification of Genes Involved in Selenium Metabolism: Evidence for a Third Selenium Utilization Trait (2008)

Zhang, Yan, Turanov, Anton, Hatfield, Dolph, Gladyshev, Vadim N.

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...

Reduced Reliance on the Trace Element Selenium During Evolution of Mammals (2008)

Lobanov, Alexey, Hatfield, Dolph, Gladyshev, Vadim N.

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...

Functional Characterization of Alternatively Spliced Human SECISBP2 Transcript Variants (2008)

Papp, Laura V., Wang, Junning, Kennedy, Derek, Boucher, Didier, Zhang, Yan, Gladyshev, Vadim N., ...

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...

SelenoDB 1.0 : A Database of Selenoprotein Genes, Proteins and SECIS Elements (2008)

Castellano, Sergi, Gladyshev, Vadim N., Guigo, Roderic, Berry, Marla J.

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...

Selenoproteinless Animals: Selenophosphate Synthetase SPS1 Functions in a Pathway Unrelated to Selenocysteine Biosynthesis (2008)

Lobanov, Alexey V., Hatfield, Dolph, Gladyshev, Vadim N.

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...

Trends in Selenium Utilization in Marine Microbial World Revealed through the Analysis of the Global Ocean Sampling (GOS) Project (2008)

Zhang, Yan, Gladyshev, Vadim N.

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...

A Functional Link between Housekeeping Selenoproteins and Phase II Enzymes (2008)

Sengupta, Aniruddha, Carlson, Bradley A., Weaver, James A., Novoselov, Sergey V., Fomenko, Dmitri E., Gladyshev, Vadim N., ...

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...

Functional characterization of alternatively spliced human SECISBP2 transcript variants (2008)

Papp, Laura V., Wang, Junning, Kennedy, Derek, Boucher, Didier, Zhang, Yan, Gladyshev, Vadim N., ...

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...

Functional characterization of alternatively spliced human SECISBP2 transcript variants (2008)

Papp, Laura V., Wang, Junning, Kennedy, Derek, Boucher, Didier, Zhang, Yan, Gladyshev, Vadim N., ...

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...

Functional characterization of alternatively spliced human SECISBP2 transcript variants (2008)

Papp, Laura V., Wang, Junning, Kennedy, Derek, Boucher, Didier, Zhang, Yan, Gladyshev, Vadim N., ...

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...

SelenoDB 1.0 : a database of selenoprotein genes, proteins and SECIS elements (2008)

Castellano, Sergi, Gladyshev, Vadim N., Guigó, Roderic, Berry, Marla J.

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...

Selenoproteinless animals: Selenophosphate synthetase SPS1 functions in a pathway unrelated to selenocysteine biosynthesis (2008)

Lobanov, Alexey V., Hatfield, Dolph L., Gladyshev, Vadim N.

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...

Solution Structure of Selenoprotein W and NMR Analysis of Its Interaction with 14-3-3 Proteins (2007)

Aachmann, Finn L., Fomenko, Dmitri E., Soragni, Alice, Gladyshev, Vadim N., Dikiy, Alexander

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...

New Techniques for Generation and Analysis of Evolutionary Trees (2007)

Chang Wang, Stephen D. Scott, Qingping Tao, Dmitri E. Fomenko, Vadim N. Gladyshev

We introduce new distance measures for the construction and analysis of phylogenies, focusing on thioredoxin-fold proteins. Our distance measures for tree construction are based on several criteria,...

Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life (2007)

Lobanov, Alexey V., Fomenko, Dmitri E., Zhang, Yan, Sengupta, Aniruddha, Hatfield, Dolph L., Gladyshev, Vadim N.

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...

The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions (2007)

Merchant, Sabeeha S., Prochnik, Simon E., Vallon, Olivier, Harris, Elizabeth H., Karpowicz, Steven J., Witman, George B., ...

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...

New Developments in Selenium Biochemistry: Selenocysteine Biosynthesis in Eukaryotes and Archaea (2007)

Xu, Xue-Ming, Carlson, Bradley A., Zhang, Yan, Mix, Heiko, Kryukov, Gregory V., Glass, Richard S., ...

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,...

Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life (2007)

Lobanov, Alexey V, Fomenko, Dmitri E, Zhang, Yan, Sengupta, Aniruddha, Hatfield, Dolph L, Gladyshev, Vadim N

Abstract 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...

SELECTIVE RESTORATION OF THE SELENOPROTEIN POPULATION IN A MOUSE HEPATOCYTE SELENOPROTEINLESS BACKGROUND WITH DIFFERENT MUTANT SELENOCYSTEINE tRNAs LACKING (2007)

Carlson, Bradley A., Moustafa, Mohamed E., Sengupta, Aniruddha, Schweizer, Ulrich, Shrimali, Rajeev, Rao, Mahadev, ...

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...

High content of proteins containing 21st and 22nd amino acids, selenocysteine and pyrrolysine, in a symbiotic deltaproteobacterium of gutless worm Olavius algarvensis (2007)

Zhang, Yan, Gladyshev, Vadim N.

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...

Identification and characterization of a selenoprotein family containing a diselenide bond in a redox motif (2007)

Shchedrina, Valentina A., Novoselov, Sergey V., Malinouski, Mikalai I., Gladyshev, Vadim N.

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....

High content of proteins containing 21st and 22nd amino acids, selenocysteine and pyrrolysine, in a symbiotic deltaproteobacterium of gutless worm Olavius algarvensis (2007)

Zhang, Yan, Gladyshev, Vadim N.

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...

NMR assignments of 1H, 13C and 15N spectra of methionine sulfoxide reductase B1 from Mus musculus (2007)

Sal, Lena S., Aachmann, Finn L., Kim, Hwa-Young, Gladyshev, Vadim N., Dikiy, Alexander

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...

A new strategy for assessing selenoprotein function: siRNA knockdown/knock-in targeting the 3'-UTR (2007)

Yoo, Min-Hyuk, Xu, Xue-Ming, Turanov, Anton A., Carlson, Bradley A., Gladyshev, Vadim N., Hatfield, Dolph L.

Selenocysteine insertion into protein in mammalian cells requires RNA elements in the 3′-untranslated regions (3′-UTRs) of selenoprotein genes. The occurrence of these conserved sequences should...

Selenoprotein H Is a Nucleolar Thioredoxin-like Protein with a Unique Expression Pattern (2007)

Novoselov, Sergey V., Kryukov, Gregory V., Xu, Xue-Ming, Carlson, Bradley A., Hatfield, Dolph L., Gladyshev, Vadim N.

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...

Novel metabolism in Chlamydomonas through the lens of genomics (2007)

Grossman, Arthur R., Croft, Martin, Gladyshev, Vadim N., Merchant, Sebeeha S., Posewitz, Matthew C., Prochnik, Simon, ...

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...

The Sep15 Protein Family: Roles in Disulfide Bond Formation and Quality Control in the Endoplasmic Reticulum (2007)

Labunskyy, Vyacheslav M., Hatfield, Dolph L., Gladyshev, Vadim N.

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...

Targeting Thioredoxin Reductase 1 Reduction in Cancer Cells Inhibits Self-Sufficient Growth and DNA Replication (2007)

Yoo, Min-Hyuk, Xu, Xue-Ming, Carlson, Bradley A., Patterson, Andrew D., Gladyshev, Vadim N., Hatfield, Dolph L.

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...

Biosynthesis of Selenocysteine on Its tRNA in Eukaryotes (2007)

Xue-Ming Xu, Bradley A. Carlson, Heiko Mix, Yan Zhang, Kazima Saira, Richard S. Glass, ...

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...

The Chlamydomonas genome reveals the evolution of key animal and plant functions. (2007)

Merchant, Sabeeha S., Prochnik, Simon E., Vallon, Olivier, Harris, Elizabeth H., Karpowicz, Steven J., Witman, George B., ...

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...

SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes (2007)

Mix, Heiko, Lobanov, Alexey V., Gladyshev, Vadim N.

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...

Dynamic evolution of selenocysteine utilization in bacteria: a balance between selenoprotein loss and evolution of selenocysteine from redox active cysteine residues (2006)

Zhang, Yan, Romero, Hector, Salinas, Gustavo, Gladyshev, Vadim N

Abstract 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...

Characterization of Alternative Cytosolic Forms and Cellular Targets of Mouse Mitochondrial Thioredoxin Reductase (2006)

Turanov, Anton A., Su, Dan, Gladyshev, Vadim N.

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...

"Preface" to Selenium: Its Molecular Biology and Role in Human Health, Second Edition (2006)

Hatfield, Dolph L., Berry, Marla J., Gladyshev, Vadim N.

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...

Selenoproteins and selenoproteomes (2006)

Gladyshev, Vadim N.

In the past several years, progress in genome sequencing and development of specialized bioinformatics tools allowed efficient identification of selenocysteine-containing proteins encoded in...

Mouse models for assessing the role of selenoproteins in health and development (2006)

Carlson, Bradley A., Xu, Xue-Ming, Shrimali, Rajeev, Sengupta, Aniruddha, Yoo, Min-Hyuk, Zhong, Nianxin, ...

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...

Selenium and methionine sulfoxide reduction (2006)

Kim, Hwa-Young, Gladyshev, Vadim N.

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...

Evolution of selenocysteine decoding and the key role of selenophosphate synthetase in the pathway of selenium utilization (2006)

Salinas, Gustavo, Romero, Héctor, Xu, Xue-Ming, Carlson, Bradley A., Hatfield, Dolph L., Gladyshev, Vadim N.

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...

Selenoproteins in parasites (2006)

Salinas, Gustavo, Lobanov, Alexei V., Gladyshev, Vadim N.

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...

The 15-kDa selenoprotein (Sep15): functional analysis and role in cancer (2006)

Labunskyy, Vyacheslav M., Gladyshev, Vadim N., Hatfield, Dolph L.

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...

Mammalian and other eukaryotic selenocysteine tRNAs (2006)

Carlson, Bradley A., Xu, Xue-Ming, Shrimali, Rajeev, Sengupta, Aniruddha, Yoo, Min-Hyuk, Irons, Robert, ...

Selenocysteine (Sec) tRNA occupies a prominent position in the expression of selenoproteins as it is essential for their synthesis and it provides the means by which selenium is co-translationally...

Thioredoxin Reductase 1 Deficiency Reverses Tumor Phenotype and Tumorigenicity of Lung Carcinoma Cells (2006)

Yoo, Min-Hyuk, Xu, Xue-Ming, Carlson, Bradley A., Gladyshev, Vadim N., Hatfield, Dolph L.

Dietary selenium has potent cancer prevention activity. Both low molecular weight selenocompounds and selenoproteins are implicated in this effect. Thioredoxin reductase 1 (TR1) is one of the major...

Alternative first exon splicing regulates subcellular distribution of methionine sulfoxide reductases (2006)

Kim, Hwa-Young, Gladyshev, Vadim N

Abstract Background Methionine sulfoxide reduction is an important protein repair pathway that protects against oxidative stress, controls protein function and has a role in regulation of aging....

Identification and characterization of Fep15, a new selenocysteine-containing member of the Sep15 protein family (2006)

Novoselov, Sergey V., Hua, Deame, Lobanov, A. V., Gladyshev, Vadim N.

Sec (selenocysteine) is a rare amino acid in proteins. It is co-translationally inserted into proteins at UGA codons with the help of SECIS (Sec insertion sequence) elements. A full set of...

NMR Structures of the Selenoproteins Sep15 and SelM Reveal Redox Activity of a New Thioredoxin-like Family (2006)

Ferguson, Andrew D., Labunskyy , Vyacheslav, Fomenko, Dmitri E., Arac, Demet, Chelliah, Yogarany, Amexcua, Carlos A., ...

Selenium has significant health benefits, including potent cancer prevention activity and roles in immune function and the male reproductive system. Selenium-containing proteins, which incorporate...

Nucleic Acids Research Advance Access published December 14, 2006 SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes (2006)

Heiko Mix, Alexey V. Lobanov, Vadim N. Gladyshev

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...

The Plasmodium selenoproteome (2006)

Lobanov, Alexey V., Delgado, Cesar, Rahlfs, Stefan, Novoselov, Sergey V., Kryukov, Gregory V., Gromer, Stephan, ...

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...

Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein (2006)

Lobanov, Alexey V., Gromer, Stephan, Salinas, Gustavo, Gladyshev, Vadim N.

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...

SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes (2006)

Mix, Heiko, Lobanov, Alexey V., Gladyshev, Vadim N.

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...

Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein (2006)

Lobanov, Alexey V., Gromer, Stephan, Salinas, Gustavo, Gladyshev, Vadim N.

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...

Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein (2006)

Lobanov, Alexey V., Gromer, Stephan, Salinas, Gustavo, Gladyshev, Vadim N.

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...

SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes (2006)

Mix, Heiko, Lobanov, Alexey V., Gladyshev, Vadim N.

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...

Evidence for Direct Roles of Two Additional Factors, SECp43 and Soluble Liver Antigen, in the Selenoprotein Synthesis Machinery (2005)

Xu, Xue-Ming, Mix, Heiko, Carlson, Bradley A., Grabowski, Paula J., Gladyshev, Vadim N., Berry, Marla J., ...

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...

Different Catalytic Mechanisms in Mammalian Selenocysteine- and Cysteine-Containing Methionine-R-Sulfoxide Reductases (2005)

Hwa-Young Kim, Vadim N. Gladyshev

Altering cysteine-containing residues in a family of oxidoreductases reveals the role of selenocysteine in influencing the catalytic mechanism.

Different Catalytic Mechanisms in Mammalian Selenocysteine- and Cysteine-Containing Methionine-R-Sulfoxide Reductases (2005)

Hwa-Young Kim, Vadim N. Gladyshev

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,...

A Novel Cysteine-rich Domain of Sep15 Mediates the Interaction with UDP-glucose:Glycoprotein Glucosyltransferase (2005)

Labunskyy, Vyacheslav M., Ferguson, Andrew D., Fomenko, Dmitri E., Chelliah, Yogarany, Hatfield, Dolph L., Gladyshev, Vadim N.

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....

Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism (2005)

Biterova, Ekaterina I., Turanov, Anton A., Gladyshev, Vadim N., Barycki, Joseph J.

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...

Evolution of selenium utilization traits (2005)

Romero, Héctor, Zhang, Yan, Gladyshev, Vadim N, Salinas, Gustavo

Abstract 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...

Mammalian Selenoprotein Thioredoxin-glutathione Reductase (2005)

Su, Dan, Novoselov, Sergey V., Sun, Qi-An, Moustafa, Mohamed E., Zhou, You, Oko, Richard, ...

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...

Pyrrolysine and Selenocysteine Use Dissimilar Decoding Strategies (2005)

Zhang, Yan, Baranov, Pavel V., Atkins, John F., Gladyshev, Vadim N.

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...

The microbial selenoproteome of the Sargasso Sea (2005)

Zhang, Yan, Fomenko, Dmitri E, Gladyshev, Vadim N

Abstract 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,...

Um34 in selenocysteine tRNA is required for the expression of stress-related selenoproteins in mammals (2005)

Carlson, Bradley A., Xu, Xue-Ming, Gladyshev, Vadim N., Hatfield, Dolph L.

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...

Selective Rescue of Selenoprotein Expression in Mice Lacking a Highly Specialized Methyl Group in Selenocysteine tRNA (2005)

Carlson, Bradley A., Xu, Xue-Ming, Gladyshev, Vadim N., Hatfield, Dolph L.

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...

Nematode selenoproteome: the use of the selenocysteine insertion system to decode one codon in an animal genome? (2005)

Taskov, Kalin, Chapple, Charles, Kryukov, Gregory V., Castellano, Sergi, Lobanov, Alexey V., Korotkov, Konstantin V., ...

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 selenoproteins...

Selenocysteine insertion directed by the 3'-UTR SECIS element in Escherichia coli (2005)

Su, Dan, Li, Yehua, Gladyshev, Vadim N.

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,...

An algorithm for identification of bacterial selenocysteine insertion sequence elements and selenoprotein genes (2005)

Zhang, Yan, Gladyshev, Vadim N.

Motivation: Incorporation of selenocysteine (Sec) into proteins in response to UGA codons requires a cis-acting RNA structure, Sec insertion sequence (SECIS) element. Whereas SECIS elements in...

An algorithm for identification of bacterial selenocysteine insertion sequence elements and selenoprotein genes (2005)

Zhang, Yan, Gladyshev, Vadim N.

Motivation: Incorporation of selenocysteine (Sec) into proteins in response to UGA codons requires a cis-acting RNA structure, Sec insertion sequence (SECIS) element. Whereas SECIS elements in E....

Identification and characterization of phosphoseryl-tRNA [Ser]Sec kinase (2004)

Carlson, Bradley A., Xu, Xue-Ming, Kryukov, Gregory V., Rao, Mahadev, Berry, Marla J., Gladyshev, Vadim N., ...

In 1970, a kinase activity that phosphorylated a minor species of seryl-tRNA to form phosphoseryl-tRNA was found in rooster liver [Maenpaa, P. H. & Bernfield, M. R. (1970) Proc. Natl. Acad. Sci. USA...

The prokaryotic selenoproteome (2004)

Kryukov, Gregory V., Gladyshev, Vadim N.

In the genetic code, the UGA codon has a dual function as it encodes selenocysteine (Sec) and serves as a stop signal. However, only the translation terminator function is used in gene annotation...

Specific Excision of the Selenocysteine tRNA [Ser]Sec (Trsp) Gene in Mouse Liver Demonstrates an Essential Role of Selenoproteins in Liver Function (2004)

Carlson, Bradley A., Novoselov, Sergey V., Kumaraswamy, Easwari, Jae Lee, Byeong, Anver, Miriam R., Gladyshev, Vadim N., ...

Selenium is essential in mammalian embryonic development. However, in adults, selenoprotein levels in several organs including liver can be substantially reduced by selenium deficiency without any...

A Study in Modeling Low-Conservation Protein Superfamilies (2004)

Wang, Chang, Scott, Stephen, Zhang, Jun, Tao, Qingping, Fomenko, Dmitri E., Gladyshev, Vadim N.

We present several algorithms for identification of new proteins in superfamilies with low primary sequence conservation. The low conservation of primary sequence in protein superfamilies such as...

Reconsidering the evolution of eukaryotic selenoproteins: a novel nonmammalian family with scattered phylogenetic distribution (2004)

Castellano, Sergi, Novoselov, Sergey V., Kryukov, Gregory V., Lescure, Alain, Blanco, Enrique, Krol, Alain, ...

While the genome sequence and gene content are available for an increasing number of organisms, eukaryotic selenoproteins remain poorly characterized. The dual role of the UGA codon confounds the...

Reconsidering the evolution of eukaryotic selenoproteins: a novel nonmammalian family with scattered phylogenetic distribution (2004)

Castellano, Sergi, Novoselov, Sergey V., Kryukov, Gregory V., Lescure, Alain, Blanco, Enrique, Krol, Alain, ...

While the genome sequence and gene content are available for an increasing number of organisms, eukaryotic selenoproteins remain poorly characterized. The dual role of the UGA codon confounds the...

A Study in Modeling Low-Conservation Protein Superfamilies (2004)

Wang, Chang, Scott, Stephen, Zhang, Jun, Tao, Qingping, Fomenko, Dmitri E., Gladyshev, Vadim N.

We present several algorithms for identification of new proteins in superfamilies with low primary sequence conservation. The low conservation of primary sequence in protein superfamilies such as...

A study in modeling low-conservation protein superfamilies (2004)

Chang Wang, Student Member, Stephen D. Scott, Jun Zhang, Qingping Tao, Dmitri E. Fomenko, ...

We present several algorithms for identification of new proteins in superfamilies with low primary sequence conservation. The low conservation of primary sequence in protein superfamilies such as...

Characterization of Mammalian Selenoproteomes (2003)

Kryukov, Gregory V., Castellano, Sergi, Novoselov, Sergey V., Lobanov, Alexey V., Zehtab, Omid, Guigo, Roderic, ...

In the genetic code, UGA serves as a stop signal and a selenocysteine codon, but no computational methods for identifying its coding function are available. Consequently, most selenoprotein genes are...

On Modeling Protein Superfamilies with Low Primary Sequence Conservation (2003)

Scott, Stephen, Ji, H., Wen, P., Fomenko, Dmitri E., Gladyshev, Vadim N.

We present several algorithms for identifying thioredoxin (Trx)-fold proteins containing a conserved CxxC motif (two cysteines separated by two residues). The low conservation of primary sequence in...

Non-animal origin of animal thioredoxin reductases: Implications for selenocysteine evolution and evolution of protein function through carboxy-terminal extensions (2003)

Novoselov, Sergey V., Gladyshev, Vadim N.

Thioredoxin reductase (TR) and thioredoxin constitute a major cellular redox system present in all organisms. In contrast to a single form of thioredoxin, there are two TR types: One (bacterial type...

Reaction Mechanism, Evolutionary Analysis, and Role of Zinc in Drosophila Methionine-R-sulfoxide Reductase (2002)

Kumar, R. Abhilash, Koc, Ahmet, Cerny, Ronald, Gladyshev, Vadim N.

Methionine residues in proteins are susceptible to oxidation, and the resulting methionine sulfoxides can be reduced back to methionines by methionine- S-sulfoxide reductase (MsrA) and...

CxxS: Fold-independent redox motif revealed by genome-wide searches for thiol/disulfide oxidoreductase function (2002)

Fomenko, Dmitri E., Gladyshev, Vadim N.

Redox reactions involving thiol groups in proteins are major participants in cellular redox regulation and antioxidant defense. Although mechanistically similar, thiol-dependent redox processes are...

Selenium Metabolism in Drosophila (2001)

Martin-Romero, F. Javier, Kryukov, Gregory V., Lobanov, Alexei V., Carlson, Bradley A., Lee, Byeong Jae, Gladyshev, Vadim N., ...

Selenocysteine is a rare amino acid in protein that is encoded by UGA with the requirement of a downstream mRNA stem-loop structure, the selenocysteine insertion sequence element. To detect...

Identification and Characterization of a New Mammalian Glutaredoxin (Thioltransferase), Grx2 (2001)

Gladyshev, Vadim N., Liu, Aimin, Novoselov, Sergey V., Krysan, Konstantin, Sun, Qi-An, Kryukov, Valentin M., ...

A thiol/disulfide oxidoreductase component of the GSH system, glutaredoxin (Grx), is involved in the reduction of GSH-based mixed disulfides and participates in a variety of cellular redox pathways....

Association between the 15-kDa Selenoprotein and UDP-glucose:Glycoprotein Glucosyltransferase in the Endoplasmic Reticulum of Mammalian Cells (2001)

Korotkov, Konstantin V., Kumaraswamy, Easwari, Zhou, You, Hatfield, Dolph L., Gladyshev, Vadim N.

Mammalian selenocysteine-containing proteins characterized with respect to function are involved in redox processes and exhibit distinct expression patterns and cellular locations. A recently...

Heterogeneity within Animal Thioredoxin Reductases (2001)

Sun, Qi-An, Zappacosta, Francesca, Factor, Valentina M., Wirth, Peter J., Hatfield, Dolph L., Gladyshev, Vadim N.

Animal thioredoxin reductases (TRs) are selenocysteine- containing flavoenzymes that utilize NADPH for reduction of thioredoxins and other protein and nonprotein substrates. Three types of mammalian...

Structure-Expression Relationships of the 15-kDa Selenoprotein Gene (2000)

Kumaraswamy, Easwari, Malyhk, Andrey, Korotkov, Konstantin V., Kozyavkin, Sergei, Hu, Yajun, Lee, Byeong J., ...

Selenium has been implicated in cancer prevention, but the mechanism and possible involvement of selenoproteins in this process are not understood. To elucidate whether the 15-kDa selenoprotein may...

New Mammalian Selenocysteine-containing Proteins Identified with an Algorithm That Searches for Selenocysteine Insertion Sequence Elements (1999)

Kryukov, Gregory V., Kryukov, Valentin M., Gladyshev, Vadim N.

Mammalian selenium-containing proteins identified thus far contain selenium in the form of a selenocysteine residue encoded by UGA. These proteins lack common amino acid sequence motifs, but...

Redox Regulation of Cell Signaling by Selenocysteine in Mammalian Thioredoxin Reductases (1999)

Sun, Qi-An, Wu, Yalin, Zappacosta, Francesca, Jeang, Kuan-Teh, Jae Lee, Byeong, Hatfield, Dolph L., ...

The intracellular generation of reactive oxygen species, together with the thioredoxin and glutathione systems, is thought to participate in redox signaling in mammalian cells. The activity of...

Selenocysteine-Containing Proteins in Mammals (1998)

Gladyshev, Vadim N., Hatfield, Dolph L.

Since the recent discovery of selenocysteine as the 21st amino acid in protein, the field of selenium biology has rapidly expanded. Twelve mammalian selenoproteins have been characterized to date and...

A New Human Selenium-containing Protein (1998)

Gladyshev, Vadim N., Jeang, Kuan Teh, Wootton, John C., Hatfield, Dolph L.

Selenium which occurs in proteins as the amino acid, selenocysteine, is essential for numerous biological processes and for human health. A prominent 75Se-labeled protein detected in human T-cells...

Characterization of Crystalline Formate Dehydrogenase H from Escherichia coli (1996)

Gladyshev, Vadim N., Boyington, Jeffrey C., Khangulov, Sergei V., Grahame, David, Stadtman, Thressa C., Sun, Peter D.

The selenocysteine-containing formate dehydrogenase H (FDH) is an 80-kDa component of the Escherichia coli formate-hydrogen lyase complex. The molybdenumcoordinated selenocysteine is essential for...

Levels of major selenoproteins in T cells decrease during HIV infection and low molecular mass selenium compounds increase

Gladyshev, Vadim N., Stadtman, Thressa C., Hatfield, Dolph L., Jeang, Kuan-Teh

It has been observed previously that plasma selenium and glutathione levels are subnormal in HIV-infected individuals, and plasma glutathione peroxidase activity is decreased. Under these conditions...

Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems

Sun, Qi-An, Kirnarsky, Leo, Sherman, Simon, Gladyshev, Vadim N.

Thioredoxin (Trx) and glutathione (GSH) systems are considered to be two major redox systems in animal cells. They are reduced by NADPH via Trx reductase (TR) or oxidized GSH (GSSG) reductase and...

Selective Inhibition of Selenocysteine tRNA Maturation and Selenoprotein Synthesis in Transgenic Mice Expressing Isopentenyladenosine-Deficient Selenocysteine tRNA

Moustafa, Mohamed E., Carlson, Bradley A., El-Saadani, Muhammad A., Kryukov, Gregory V., Sun, Qi-An, Harney, John W., ...

Selenocysteine (Sec) tRNA (tRNA[Ser]Sec) serves as both the site of Sec biosynthesis and the adapter molecule for donation of this amino acid to protein. The consequences on selenoprotein...

Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase

Kryukov, Gregory V., Kumar, R. Abhilash, Koc, Ahmet, Sun, Zhaohui, Gladyshev, Vadim N.

Selenoprotein R (SelR) is a mammalian selenocysteine-containing protein with no known function. Here we report that cysteine homologs of SelR are present in all organisms except certain parasites and...

Selenoproteins and selenocysteine insertion system in the model plant cell system, Chlamydomonas reinhardtii

Novoselov, Sergey V., Rao, Mahadev, Onoshko, Natalia V., Zhi, Huijun, Kryukov, Gregory V., Xiang, Youbin, ...

Known eukaryotic selenocysteine (Sec)-containing proteins are animal proteins, whereas selenoproteins have not been found in yeast and plants. Surprisingly, we detected selenoproteins in a member of...

Mammalian Selenoprotein in Which Selenocysteine (Sec) Incorporation Is Supported by a New Form of Sec Insertion Sequence Element

Korotkov, Konstantin V., Novoselov, Sergey V., Hatfield, Dolph L., Gladyshev, Vadim N.

Selenocysteine (Sec), the 21st amino acid in protein, is encoded by UGA. The Sec insertion sequence (SECIS) element, which is the stem-loop structure present in 3" untranslated regions (UTRs) of...

Selective Removal of the Selenocysteine tRNA[Ser]Sec Gene (Trsp) in Mouse Mammary Epithelium

Kumaraswamy, Easwari, Carlson, Bradley A., Morgan, Fanta, Miyoshi, Keiko, Robinson, Gertraud W., Su, Dan, ...

Mice homozygous for an allele encoding the selenocysteine (Sec) tRNA[Ser]Sec gene (Trsp) flanked by loxP sites were generated. Cre recombinase-dependent removal of Trsp in these mice was lethal to...

The Drosophila Selenoprotein BthD Is Required for Survival and Has a Role in Salivary Gland Development

Kwon, So Yeon, Badenhorst, Paul, Martin-Romero, F. Javier, Carlson, Bradley A., Paterson, Bruce M., Gladyshev, Vadim N., ...

Selenium is implicated in many diseases, including cancer, but its function at the molecular level is poorly understood. BthD is one of three selenoproteins recently identified in Drosophila. To...

Methionine Sulfoxide Reduction in Mammals: Characterization of Methionine-R-Sulfoxide Reductases

Kim, Hwa-Young, Gladyshev, Vadim N.

Methionine residues in proteins are susceptible to oxidation by reactive oxygen species, but can be repaired via reduction of the resulting methionine sulfoxides by methionine-S-sulfoxide reductase...

Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging

Koc, Ahmet, Gasch, Audrey P., Rutherford, Julian C., Kim, Hwa-Young, Gladyshev, Vadim N.

Aging is thought to be caused by the accumulation of damage, primarily from oxidative modifications of cellular components by reactive oxygen species (ROS). Here we used yeast methionine sulfoxide...

Identification and characterization of phosphoseryl-tRNA[Ser]Sec kinase

Carlson, Bradley A., Xu, Xue-Ming, Kryukov, Gregory V., Rao, Mahadev, Berry, Marla J., Gladyshev, Vadim N., ...

In 1970, a kinase activity that phosphorylated a minor species of seryl-tRNA to form phosphoseryl-tRNA was found in rooster liver [Maenpaa, P. H. & Bernfield, M. R. (1970) Proc. Natl. Acad. Sci. USA...

Nematode selenoproteome: the use of the selenocysteine insertion system to decode one codon in an animal genome?

Taskov, Kalin, Chapple, Charles, Kryukov, Gregory V., Castellano, Sergi, Lobanov, Alexey V., Korotkov, Konstantin V., ...

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 selenoproteins...

Selenocysteine insertion directed by the 3′-UTR SECIS element in Escherichia coli

Su, Dan, Li, Yehua, Gladyshev, Vadim N.

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,...

The microbial selenoproteome of the Sargasso Sea

Zhang, Yan, Fomenko, Dmitri E, Gladyshev, Vadim N

An analysis of the selenoproteome of the largest microbial sequence dataset, the Sargasso Sea environmental genome sequences, identified 310 selenoprotein genes that clustered into 25 families. This...

Evolution of selenium utilization traits

Romero, Héctor, Zhang, Yan, Gladyshev, Vadim N, Salinas, Gustavo

Completely sequenced genomes were analyzed for occurrence of SelA, B, C, D and ybbB genes. SelB and SelC were found to be signatures for the Sec decoding trait, while SelD defines the overall...

Different Catalytic Mechanisms in Mammalian Selenocysteine- and Cysteine-Containing Methionine-R-Sulfoxide Reductases

Kim, Hwa-Young, Gladyshev, Vadim N

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,...

Reconsidering the evolution of eukaryotic selenoproteins: a novel nonmammalian family with scattered phylogenetic distribution

Castellano, Sergi, Novoselov, Sergey V, Kryukov, Gregory V, Lescure, Alain, Blanco, Enrique, Krol, Alain, ...

While the genome sequence and gene content are available for an increasing number of organisms, eukaryotic selenoproteins remain poorly characterized. The dual role of the UGA codon confounds the...

The prokaryotic selenoproteome

Kryukov, Gregory V, Gladyshev, Vadim N

In the genetic code, the UGA codon has a dual function as it encodes selenocysteine (Sec) and serves as a stop signal. However, only the translation terminator function is used in gene annotation...

The Plasmodium selenoproteome

Lobanov, Alexey V., Delgado, Cesar, Rahlfs, Stefan, Novoselov, Sergey V., Kryukov, Gregory V., Gromer, Stephan, ...

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...

Chlamydomonas reinhardtii selenocysteine tRNA[Ser]Sec

RAO, MAHADEV, CARLSON, BRADLEY A., NOVOSELOV, SERGEY V., WEEKS, DONALD P., GLADYSHEV, VADIM N., HATFIELD, DOLPH L.

Eukaryotic selenocysteine (Sec) protein insertion machinery was thought to be restricted to animals, but the occurrence of both Sec-containing proteins and the Sec insertion system was recently found...

Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism

Biterova, Ekaterina I., Turanov, Anton A., Gladyshev, Vadim N., Barycki, Joseph J.

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...

Diversity and functional plasticity of eukaryotic selenoproteins: Identification and characterization of the SelJ family

Castellano, Sergi, Lobanov, Alexey V., Chapple, Charles, Novoselov, Sergey V., Albrecht, Mario, Hua, Deame, ...

Selenoproteins are a diverse group of proteins that contain selenocysteine (Sec), the 21st amino acid. In the genetic code, UGA serves as a termination signal and a Sec codon. This dual role has...

Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein

Lobanov, Alexey V., Gromer, Stephan, Salinas, Gustavo, Gladyshev, Vadim N.

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...

Levels of major selenoproteins in T cells decrease during HIV infection and low molecular mass selenium compounds increase

Gladyshev, Vadim N., Stadtman, Thressa C., Hatfield, Dolph L., Jeang, Kuan-Teh

It has been observed previously that plasma selenium and glutathione levels are subnormal in HIV-infected individuals, and plasma glutathione peroxidase activity is decreased. Under these conditions...

Selenoprotein oxidoreductase with specificity for thioredoxin and glutathione systems

Sun, Qi-An, Kirnarsky, Leo, Sherman, Simon, Gladyshev, Vadim N.

Thioredoxin (Trx) and glutathione (GSH) systems are considered to be two major redox systems in animal cells. They are reduced by NADPH via Trx reductase (TR) or oxidized GSH (GSSG) reductase and...

Selective Inhibition of Selenocysteine tRNA Maturation and Selenoprotein Synthesis in Transgenic Mice Expressing Isopentenyladenosine-Deficient Selenocysteine tRNA

Moustafa, Mohamed E., Carlson, Bradley A., El-Saadani, Muhammad A., Kryukov, Gregory V., Sun, Qi-An, Harney, John W., ...

Selenocysteine (Sec) tRNA (tRNA[Ser]Sec) serves as both the site of Sec biosynthesis and the adapter molecule for donation of this amino acid to protein. The consequences on selenoprotein...

Selenoprotein R is a zinc-containing stereo-specific methionine sulfoxide reductase

Kryukov, Gregory V., Kumar, R. Abhilash, Koc, Ahmet, Sun, Zhaohui, Gladyshev, Vadim N.

Selenoprotein R (SelR) is a mammalian selenocysteine-containing protein with no known function. Here we report that cysteine homologs of SelR are present in all organisms except certain parasites and...

Selenoproteins and selenocysteine insertion system in the model plant cell system, Chlamydomonas reinhardtii

Novoselov, Sergey V., Rao, Mahadev, Onoshko, Natalia V., Zhi, Huijun, Kryukov, Gregory V., Xiang, Youbin, ...

Known eukaryotic selenocysteine (Sec)-containing proteins are animal proteins, whereas selenoproteins have not been found in yeast and plants. Surprisingly, we detected selenoproteins in a member of...

Mammalian Selenoprotein in Which Selenocysteine (Sec) Incorporation Is Supported by a New Form of Sec Insertion Sequence Element

Korotkov, Konstantin V., Novoselov, Sergey V., Hatfield, Dolph L., Gladyshev, Vadim N.

Selenocysteine (Sec), the 21st amino acid in protein, is encoded by UGA. The Sec insertion sequence (SECIS) element, which is the stem-loop structure present in 3" untranslated regions (UTRs) of...

Selective Removal of the Selenocysteine tRNA[Ser]Sec Gene (Trsp) in Mouse Mammary Epithelium

Kumaraswamy, Easwari, Carlson, Bradley A., Morgan, Fanta, Miyoshi, Keiko, Robinson, Gertraud W., Su, Dan, ...

Mice homozygous for an allele encoding the selenocysteine (Sec) tRNA[Ser]Sec gene (Trsp) flanked by loxP sites were generated. Cre recombinase-dependent removal of Trsp in these mice was lethal to...

The Drosophila Selenoprotein BthD Is Required for Survival and Has a Role in Salivary Gland Development

Kwon, So Yeon, Badenhorst, Paul, Martin-Romero, F. Javier, Carlson, Bradley A., Paterson, Bruce M., Gladyshev, Vadim N., ...

Selenium is implicated in many diseases, including cancer, but its function at the molecular level is poorly understood. BthD is one of three selenoproteins recently identified in Drosophila. To...

Methionine Sulfoxide Reduction in Mammals: Characterization of Methionine-R-Sulfoxide Reductases

Kim, Hwa-Young, Gladyshev, Vadim N.

Methionine residues in proteins are susceptible to oxidation by reactive oxygen species, but can be repaired via reduction of the resulting methionine sulfoxides by methionine-S-sulfoxide reductase...

Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging

Koc, Ahmet, Gasch, Audrey P., Rutherford, Julian C., Kim, Hwa-Young, Gladyshev, Vadim N.

Aging is thought to be caused by the accumulation of damage, primarily from oxidative modifications of cellular components by reactive oxygen species (ROS). Here we used yeast methionine sulfoxide...

Identification and characterization of phosphoseryl-tRNA[Ser]Sec kinase

Carlson, Bradley A., Xu, Xue-Ming, Kryukov, Gregory V., Rao, Mahadev, Berry, Marla J., Gladyshev, Vadim N., ...

In 1970, a kinase activity that phosphorylated a minor species of seryl-tRNA to form phosphoseryl-tRNA was found in rooster liver [Maenpaa, P. H. & Bernfield, M. R. (1970) Proc. Natl. Acad. Sci. USA...

Nematode selenoproteome: the use of the selenocysteine insertion system to decode one codon in an animal genome?

Taskov, Kalin, Chapple, Charles, Kryukov, Gregory V., Castellano, Sergi, Lobanov, Alexey V., Korotkov, Konstantin V., ...

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 selenoproteins...

Selenocysteine insertion directed by the 3′-UTR SECIS element in Escherichia coli

Su, Dan, Li, Yehua, Gladyshev, Vadim N.

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,...

The microbial selenoproteome of the Sargasso Sea

Zhang, Yan, Fomenko, Dmitri E, Gladyshev, Vadim N

An analysis of the selenoproteome of the largest microbial sequence dataset, the Sargasso Sea environmental genome sequences, identified 310 selenoprotein genes that clustered into 25 families. This...

Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism

Biterova, Ekaterina I., Turanov, Anton A., Gladyshev, Vadim N., Barycki, Joseph J.

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...

Evolution of selenium utilization traits

Romero, Héctor, Zhang, Yan, Gladyshev, Vadim N, Salinas, Gustavo

Completely sequenced genomes were analyzed for occurrence of SelA, B, C, D and ybbB genes. SelB and SelC were found to be signatures for the Sec decoding trait, while SelD defines the overall...

Different Catalytic Mechanisms in Mammalian Selenocysteine- and Cysteine-Containing Methionine-R-Sulfoxide Reductases

Kim, Hwa-Young, Gladyshev, Vadim N

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,...

Diversity and functional plasticity of eukaryotic selenoproteins: Identification and characterization of the SelJ family

Castellano, Sergi, Lobanov, Alexey V., Chapple, Charles, Novoselov, Sergey V., Albrecht, Mario, Hua, Deame, ...

Selenoproteins are a diverse group of proteins that contain selenocysteine (Sec), the 21st amino acid. In the genetic code, UGA serves as a termination signal and a Sec codon. This dual role has...

Reconsidering the evolution of eukaryotic selenoproteins: a novel nonmammalian family with scattered phylogenetic distribution

Castellano, Sergi, Novoselov, Sergey V, Kryukov, Gregory V, Lescure, Alain, Blanco, Enrique, Krol, Alain, ...

While the genome sequence and gene content are available for an increasing number of organisms, eukaryotic selenoproteins remain poorly characterized. The dual role of the UGA codon confounds the...

The prokaryotic selenoproteome

Kryukov, Gregory V, Gladyshev, Vadim N

In the genetic code, the UGA codon has a dual function as it encodes selenocysteine (Sec) and serves as a stop signal. However, only the translation terminator function is used in gene annotation...

The Plasmodium selenoproteome

Lobanov, Alexey V., Delgado, Cesar, Rahlfs, Stefan, Novoselov, Sergey V., Kryukov, Gregory V., Gromer, Stephan, ...

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...

Chlamydomonas reinhardtii selenocysteine tRNA[Ser]Sec

RAO, MAHADEV, CARLSON, BRADLEY A., NOVOSELOV, SERGEY V., WEEKS, DONALD P., GLADYSHEV, VADIM N., HATFIELD, DOLPH L.

Eukaryotic selenocysteine (Sec) protein insertion machinery was thought to be restricted to animals, but the occurrence of both Sec-containing proteins and the Sec insertion system was recently found...

Selenium metabolism in Trypanosoma: characterization of selenoproteomes and identification of a Kinetoplastida-specific selenoprotein

Lobanov, Alexey V., Gromer, Stephan, Salinas, Gustavo, Gladyshev, Vadim N.

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...

Biosynthesis of Selenocysteine on Its tRNA in Eukaryotes

Xu, Xue-Ming, Carlson, Bradley A, Mix, Heiko, Zhang, Yan, Saira, Kazima, Glass, Richard S, ...

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...

Dynamic evolution of selenocysteine utilization in bacteria: a balance between selenoprotein loss and evolution of selenocysteine from redox active cysteine residues

Zhang, Yan, Romero, Hector, Salinas, Gustavo, Gladyshev, Vadim N

Comparative genomics and evolutionary analyses to examine the dynamics of selenocysteine utilization in bacteria reveal a dynamic balance between selenoprotein origin and loss.

SECIS elements in the coding regions of selenoprotein transcripts are functional in higher eukaryotes

Mix, Heiko, Lobanov, Alexey V., Gladyshev, Vadim N.

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...

High content of proteins containing 21st and 22nd amino acids, selenocysteine and pyrrolysine, in a symbiotic deltaproteobacterium of gutless worm Olavius algarvensis

Zhang, Yan, Gladyshev, Vadim N.

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...

Targeting Thioredoxin Reductase 1 Reduction in Cancer Cells Inhibits Self-Sufficient Growth and DNA Replication

Yoo, Min-Hyuk, Xu, Xue-Ming, Carlson, Bradley A., Patterson, Andrew D., Gladyshev, Vadim N., Hatfield, Dolph L.

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...

A highly efficient form of the selenocysteine insertion sequence element in protozoan parasites and its use in mammalian cells

Novoselov, Sergey V., Lobanov, Alexey V., Hua, Deame, Kasaikina, Marina V., Hatfield, Dolph L., Gladyshev, Vadim N.

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...

A new strategy for assessing selenoprotein function: siRNA knockdown/knock-in targeting the 3′-UTR

Yoo, Min-Hyuk, Xu, Xue-Ming, Turanov, Anton A., Carlson, Bradley A., Gladyshev, Vadim N., Hatfield, Dolph L.

Selenocysteine insertion into protein in mammalian cells requires RNA elements in the 3′-untranslated regions (3′-UTRs) of selenoprotein genes. The occurrence of these conserved sequences should...

Comparative Genomic Analyses of Copper Transporters and Cuproproteomes Reveal Evolutionary Dynamics of Copper Utilization and Its Link to Oxygen

Ridge, Perry G., Zhang, Yan, Gladyshev, Vadim N.

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...

SelenoDB 1.0 : a database of selenoprotein genes, proteins and SECIS elements

Castellano, Sergi, Gladyshev, Vadim N., Guigó, Roderic, Berry, Marla J.

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...

Identification and characterization of a selenoprotein family containing a diselenide bond in a redox motif

Shchedrina, Valentina A., Novoselov, Sergey V., Malinouski, Mikalai Yu., Gladyshev, Vadim N.

Selenocysteine (Sec, U) insertion into proteins is directed by translational recoding of specific UGA codons located upstream of a stem-loop structure known as Sec insertion sequence (SECIS) element....

Non-animal origin of animal thioredoxin reductases: Implications for selenocysteine evolution and evolution of protein function through carboxy-terminal extensions

Novoselov, Sergey V., Gladyshev, Vadim N.

Thioredoxin reductase (TR) and thioredoxin constitute a major cellular redox system present in all organisms. In contrast to a single form of thioredoxin, there are two TR types: One (bacterial type...

Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life

Lobanov, Alexey V, Fomenko, Dmitri E, Zhang, Yan, Sengupta, Aniruddha, Hatfield, Dolph L, Gladyshev, Vadim N

In silico and metabolic labeling studies of the selenoproteomes of several eukaryotes revealed distinct selenoprotein patterns as well as an ancient origin of selenoproteins and massive, independent...

CxxS: Fold-independent redox motif revealed by genome-wide searches for thiol/disulfide oxidoreductase function

Fomenko, Dmitri E., Gladyshev, Vadim N.

Redox reactions involving thiol groups in proteins are major participants in cellular redox regulation and antioxidant defense. Although mechanistically similar, thiol-dependent redox processes are...

Reduced reliance on the trace element selenium during evolution of mammals

Lobanov, Alexey V, Hatfield, Dolph L, Gladyshev, Vadim N

Evolution from fish to mammals was accompanied by decreased use of selenocysteine, raising questions about the need for selenium dietary supplements when pathology is not imminent.

Trends in Selenium Utilization in Marine Microbial World Revealed through the Analysis of the Global Ocean Sampling (GOS) Project

Zhang, Yan, Gladyshev, Vadim N.

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...

Selenoproteinless animals: Selenophosphate synthetase SPS1 functions in a pathway unrelated to selenocysteine biosynthesis

Lobanov, Alexey V., Hatfield, Dolph L., Gladyshev, Vadim N.

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...

Functional characterization of alternatively spliced human SECISBP2 transcript variants

Papp, Laura V., Wang, Junning, Kennedy, Derek, Boucher, Didier, Zhang, Yan, Gladyshev, Vadim N., ...

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...

A Structure-Based Approach for Detection of Thiol Oxidoreductases and Their Catalytic Redox-Active Cysteine Residues

Marino, Stefano M., Gladyshev, Vadim N.

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...

Platyhelminth Mitochondrial and Cytosolic Redox Homeostasis Is Controlled by a Single Thioredoxin Glutathione Reductase and Dependent on Selenium and Glutathione*S⃞

Bonilla, Mariana, Denicola, Ana, Novoselov, Sergey V., Turanov, Anton A., Protasio, Anna, Izmendi, Darwin, ...

Platyhelminth parasites are a major health problem in developing countries. In contrast to their mammalian hosts, platyhelminth thiol-disulfide redox homeostasis relies on linked...

Selenoproteins Mediate T Cell Immunity through an Antioxidant Mechanism*S⃞

Shrimali, Rajeev K., Irons, Robert D., Carlson, Bradley A., Sano, Yasuyo, Gladyshev, Vadim N., Park, Jin Mo, ...

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...

Mammals Reduce Methionine-S-sulfoxide with MsrA and Are Unable to Reduce Methionine-R-sulfoxide, and This Function Can Be Restored with a Yeast Reductase*S⃞

Lee, Byung Cheon, Le, Dung Tien, Gladyshev, Vadim N.

Methionine is an essential amino acid in mammals at the junction of methylation, protein synthesis, and sulfur pathways. However, this amino acid is highly susceptible to oxidation, resulting in a...