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Articles 1 - 13 of 13
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
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 of …
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
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
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 locations in …
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
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 …
Eukaryotic Selenoproteins And Selenoproteomes, Alexey V. Lobanov, Dolph L. Hatfield, Vadim N. Gladyshev
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 …
Comparative Genomic Analyses Of Nickel, Cobalt And Vitamin B12 Utilization, Yan Zhang, Dmitry Rodionov, Mikhail Gelfand, Vadim N. Gladyshev
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 …
Functions And Evolution Of Selenoprotein Methionine Sulfoxide Reductases, Byung Cheon Lee, Alexander Dikiy, Hwa-Young Kim, Vadim N. Gladyshev
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 catalytic advantage …
Selenoproteins That Function In Cancer Prevention And Promotion, Dolph L. Hatfield, Min-Hyuk Yoo, Bradley A. Carlson, Vadim N. Gladyshev
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
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 …
A Structure-Based Approach For Detection Of Thiol Oxidoreductases And Their Catalytic Redox-Active Cysteine Residues, Stefano M. Marino, Vadim N. Gladyshev
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 …
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
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
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 …
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
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 in animal …