Biochemistry, Biophysics, and Structural Biology Commons^™

Role Of Activator Protein-1 In The Down-Regulation Of The Human Cyp2j2 Gene In Hypoxia, Nicole Y. Marden, Eva Fiala-Beer, Shi-Hua Xiang, Michael Murray

School of Veterinary and Biomedical Sciences: Faculty Publications

The cytochrome P450 (CYP) 2J2 arachidonic acid epoxygenase gene was down-regulated at a pre-translational level in human hepatoma-derived HepG2 cells incubated in a hypoxic environment; under these conditions, the expression of c-Jun and c-Fos mRNA and protein was increased. The 5′-upstream region of the CYP2J2 gene was isolated by amplification of a 2341 bp fragment and putative regulatory elements that resembled activator protein-1 (AP-1)-like sequences were identified. From transient transfection analysis, c-Jun was found to strongly activate a CYP2J2–luciferase reporter construct, but co-transfection with plasmids encoding c-Fos or c-Fos-related antigens, Fra-1 and -2, abrogated reporter activity. Using a series …

Mucosal Priming Of Simian Immunodeficiency Virus-Specific Cytotoxic T-Lymphocyte Responses In Rhesus Macaques By The Salmonella Type Iii Secretion Antigen Delivery System, David T. Evans, Li-Mei Chen, Jacqueline Gillis, Kuei-Chin Lin, Brian Harty, Gail P. Mazzara, Ruben O. Donis, Keith G. Mansfield, Jeffrey D. Lifson, Ronald C. Desrosiers, Jorge E. Galán, R. Paul Johnson

School of Veterinary and Biomedical Sciences: Faculty Publications

Nearly all human immunodeficiency virus (HIV) infections are acquired mucosally, and the gut-associated lymphoid tissues are important sites for early virus replication. Thus, vaccine strategies designed to prime virus-specific cytotoxic T lymphocyte (CTL) responses that home to mucosal compartments may be particularly effective at preventing or containing HIV infection. The Salmonella type III secretion system has been shown to be an effective approach for stimulating mucosal CTL responses in mice. We therefore tested ∆phoP-phoQ attenuated strains of Salmonella enterica serovar Typhimurium and S. enterica serovar Typhi expressing fragments of the simian immunodeficiency virus (SIV) Gag protein fused to the …

Method To Detect The Presence Of A Microorganism Or Agent In An Animal, David R. Smith, Laura L. Hungerford, Rodney A. Moxley, Susanne Hinkley, Terry Klopfenstein, Jeff Gray

School of Veterinary and Biomedical Sciences: Faculty Publications

The present invention provides a method to detect the presence of a microorganism or agent in an animal. The method encompasses placement of devices at various locations where the animal resides so as to induce the animal to initiate contact with the device. As a result of this contact, the animal deposits various microorganisms and agents on the device. The device is then tested for the presence of the particular microorganism or agent of interest.

A Phylogenetic Study Of Cytochrome B561 Proteins, Wim Verelst, Han H. Asard

Department of Biochemistry: Faculty Publications

Background: As an antioxidant and cofactor to numerous metabolic enzymes, ascorbate has an essential role in plants and animals. Cytochromes b561 constitute a class of intrinsic membrane proteins involved in ascorbate regeneration. Despite their importance in ascorbate metabolism, no evolutionary analysis has been presented so far on this newly described protein family. Results: Cytochromes b561 have been identified in a large number of phylogenetically distant species, but are absent in fungi and prokaryotes. Most species contain three or four cytochrome b561 paralogous proteins, and the encoding genes usually have four or five exons. At the protein level, sequence similarities are …

Functional Copper At The Acetyl-Coa Synthase Active Site, Javier Seravalli, Welwel Gu, Annie Tam, Erick Strauss, Stephen P. Cramer, Stephen W. Ragsdale

Department of Biochemistry: Faculty Publications

The bifunctional CO dehydrogenase/acetyl-CoA synthase (CODH/ACS) plays a central role in the Wood–Ljungdahl pathway of autotrophic CO₂ fixation. A recent structure of the Moorella thermoacetica enzyme revealed that the ACS active site contains a [4Fe-4S] cluster bridged to a binuclear Cu-Ni site. Here, biochemical and x-ray absorption spectroscopic (XAS) evidence is presented that the copper ion at the M. thermoacetica ACS active site is essential. Depletion of copper correlates with reduction in ACS activity and in intensity of the ‘‘NiFeC’’ EPR signal without affecting either the activity or the EPR spectroscopic properties associated with CODH. In contrast, Zn content …

Transmembrane Movement Of Exogenous Long-Chain Fatty Acids: Proteins, Enzymes, And Vectorial Esterification, Paul N. Black, Concetta C. Dirusso

Department of Biochemistry: Faculty Publications

INTRODUCTION......................................................................................................................................................454

FATTY ACIDS AND BIOLOGICAL MEMBRANES.............................................................................................455

Fatty Acid Transport Defined ...............................................................................................................................456

MODEL SYSTEMS TO INVESTIGATE FATTY ACID TRANSPORT ..............................................................456

Genetic Foundations of Fatty Acid Transport....................................................................................................456

PROTEINS IMPLICATED IN FATTY ACID TRANSPORT ...............................................................................456

Fatty Acid Translocase..........................................................................................................................................457

Fatty Acid Binding Protein—Membrane Bound ................................................................................................457

Fatty Acid Transport Protein...............................................................................................................................458

The Long-Chain Fatty Acid Transport Protein FadL .......................................................................................458

Fatty Acyl-CoA Synthetase ...................................................................................................................................459

VECTORIAL ACYLATION: ONE MECHANISM OPERATIONAL IN FATTY ACID TRANSPORT...........460

THE BACTERIAL PARADIGM ...............................................................................................................................460

Energetics of Fatty Acid Transport in Gram-Negative Bacteria......................................................................460

The Fatty Acid Transporter FadL........................................................................................................................461

The Fatty Acyl-CoA Synthetase FadD..................................................................................................................461

Structural Considerations of FACS .....................................................................................................................462

FATTY ACID TRANSPORT AND ACTIVATION IN YEAST: …

The Many Faces Of Vitamin B12: Catalysis By Cobalamin-Dependent Enzymes, Ruma Banerjee, Stephen W. Ragsdale

Department of Biochemistry: Faculty Publications

Vitamin B₁₂ is a complex organometallic cofactor associated with three subfamilies of enzymes: the adenosylcobalamin-dependent isomerases, the methylcobalamin-dependent methyltransferases, and the dehalogenases. Different chemical aspects of the cofactor are exploited during catalysis by the isomerases and the methyltransferases. Thus, the cobalt-carbon bond ruptures homolytically in the isomerases, whereas it is cleaved heterolytically in the methyltransferases. The reaction mechanism of the dehalogenases, the most recently discovered class of B₁₂ enzymes, is poorly understood. Over the past decade our understanding of the reaction mechanisms of B₁₂ enzymes has been greatly enhanced by the availability of large amounts of enzyme …

Algal Composition And Abundance In The Neuston Surface Micro Layer From A Lake And Pond In Virginia (U.S.A.), Lubomira Burchardt, Harold G. Marshall

Biological Sciences Faculty Publications

A comparative study was conducted that characterized the algae within the neuston, ca 2 mm below the surface, and the algae in the water column from two freshwater habitats. There were significant differences in total algal abundance and the abundance of diatoms, cyanoprokaryotes, and chlorophytes between the neuston and water column algae of these two regions during each season and at both sites. The pond neuston was dominated by chlorophytes, with total algal abundance ranging seasonally from 0.6 to 59.6 x 10^-3 cells ml^-1 compared to water column algal concentrations of 4.1 to 40.4 x 10-3 cells ml-1. …

Comparative Serological And Molecular Analysis Of Group Viii Spiroplasma From Australia And North America, April Carmita Murphy

College of Graduate Studies: Theses & Dissertations (1964–2006)

Spiroplasma bacteria (Mollicutes: Spiroplasmataceae) are characterized by motility, helical morphology and are most frequently found in insect guts and phloem tubes of plants. Traditionally, Spiroplasma have been classified by serology. Recent work has generated 16S rDNA sequences that generally correlate with the serological findings. Although the serology and the 16S rDNA sequence analysis clearly classifies strains to the group level, they do not distinguish between strains within the same group. The goal of this project was to investigate the utility of the 16S-23S rDNA intergenic spacer region sequence as a means to distinguish these closely related strains.

We chose Group …

Mosquitoes, West Nile Virus, Attractants, Competition, Environmental Conditions, And Insecticide Resistance, Alan Bradley Wells

College of Graduate Studies: Theses & Dissertations (1964–2006)

The six main objectives of this project were: 1) test for levels of West Nile Virus in mosquitoes collected at a Fulton County Recreational Facility, 2) assay various mosquito oviposition attractants on West Nile virus positive female mosquitoes, 3) test effects of distance between mosquito infusion attractants, 4) determine effects of study site location, treatment, and competition distances on mosquito collections, 5) test for any correlation between environmental factors and mosquito abundance, and 6) measure levels of enzymatic insecticide resistance present in species of female mosquitoes that tested positive for the presence of West Nile Virus. Ofthe two species that …

Multiple Transporters Associated With Malaria Parasite Responses To Chloroquine And Quinine, Jianbing Mu, Michael T. Ferdig, Xiaorong Feng, Deirdre A. Joy, Junhui Duan, Tetsuya Furuya, G. Subramanian, L. Aravind, Roland A. Cooper, John C. Wootton, Momia Xiong, Xin-Zhuan Su

Biological Sciences Faculty Publications

Mutations and/or overexpression of various transporters are known to confer drug resistance in a variety of organisms. In the malaria parasite Plasmodium falciparum, a homologue of P-glycoprotein, PfMDR1, has been implicated in responses to chloroquine (CO), quinine (ON) and other drugs, and a putative transporter, PfCRT, was recently demonstrated to be the key molecule in CO resistance. However, other unknown molecules are probably involved, as different parasite clones carrying the same pfcrt and pfmdr1 alleles show a wide range of quantitative responses to CO and ON. Such molecules may contribute to increasing incidences of ON treatment failure, the molecular basis …

The Effects Of Student Manipulated Lewis Structure Models On Chemistry Achievement According To Cognitive Level, Kimberly M. Ross

Dissertations and Theses @ UNI

The purpose of this study was to determine if there was a correlation between teaching method or cognitive development and achievement in a unit on Lewis electron dot structures. Forty-six students were taught a unit on Lewis electron dot structures using the traditional paper and pencil method. Thirty-eight students were taught the same unit using a manipulative model instead of the traditional method. Both groups of students were given pre and post-tests on Lewis electron dot structures and their gains after instruction were measured. The Group Assessment of Logical Thinking measured student's cognitive level. Students were categorized as concrete, transitional …

Evidence For An Epigenetic Mechanism By Which Hsp90 Acts As A Capacitor For Morphological Evolution, Vincent E. Sollars, Xiangyi Lu, Li Xiao, Xiaoyan Wang, Mark D. Garfinkel, Douglas M. Ruden

Biochemistry and Microbiology

Morphological alterations have been shown to occur in Drosophila melanogaster when function of Hsp90 (heat shock 0-kDa protein 1α, encoded by Hsp83) is compromised during development1. Genetic selection maintains the altered phenotypes in subsequent generations1. Recent experiments have shown, however, that phenotypic variation still occurs in nearly isogenic recombinant inbred strains of Arabidopsis thaliana2. Using a sensitized isogenic D. melanogaster strain, iso-KrIf-1, we confirm this finding and present evidence supporting an epigenetic mechanism for Hsp90’s capacitor function, whereby reduced activity of Hsp90 induces a heritably altered chromatin state. The altered chromatin state is evidenced by ectopic expression …

The Insulation Of Genes From External Enhancers And Silencing Chromatin, Bonnie Burgess-Beusse, Catherine Farrell, Miklos Gaszner, Michael Litt, Vesco Mutskov, Felix Recillas - Targa, Melanie Simpson, Adam West, Gary Felsenfeld

Department of Biochemistry: Faculty Publications

Insulators are DNA sequence elements that can serve in some cases as barriers to protect a gene against the encroachment of adjacent inactive condensed chromatin. Some insulators also can act as blocking elements to protect against the activating influence of distal enhancers associated with other genes. Although most of the insulators identified so far derive from Drosophila, they also are found in vertebrates. An insulator at the 5′ end of the chicken β -globin locus marks a boundary between an open chromatin domain and a region of constitutively condensed chromatin. Detailed analysis of this element shows that it possesses …

Ccr4-Bearing T Cells Participate In Autoimmune Diabetes., Soon H. Kim, Mary M. Cleary, Howard S. Fox, Icos Coporation, Nora Sarvetnick

Journal Articles: Regenerative Medicine

Chemokine receptor expression is exquisitely regulated on T cell subsets during the course of their migration to inflammatory sites. In the present study we demonstrate that CCR4 expression marks a pathogenic population of autoimmune T cells. CCR4 was found exclusively on memory CD4(+) T cells during the progression of disease in NOD mice. Cells expressing the CCR4 ligand TARC (thymus- and activation-regulated chemokine) were detected within infiltrated islets from prediabetic mice. Interestingly, neutralization of macrophage-derived chemokine (MDC) with Ab caused a significant reduction of CCR4-positive T cells within the pancreatic infiltrates and inhibited the development of insulitis and diabetes. Furthermore, …

A Neural Network Method For Protein Classification, Arie D. Jones

All-Inclusive List of Electronic Theses and Dissertations

The investigation detailed in this paper attempts to utilize a Leaming Vector Quantization network in order to classify a set of mitochondrial proteins based upon their amino acid sequence. The Learning Vector Quantization network uses a nearest neighbor approach to classification. Input vectors are fed into the network, which produces output vectors. Those output vectors are then matched by means of a distance bias to a corresponding classification vector. The learning and test sets consisted of thirteen similar mitochodrial proteins from seventy-two different species. This provided a pool of over nine hundred proteins to use. Half of the species were …

Bioorganic Studies In Aids: Synthetic Antifungals Against Pneumocystis Carinii Based On The Multivalency Concept, Langu Peng, Cunxiang Chen, Christian R. Gonzalez, Valeria Balogh-Nair

Publications and Research

We report the syntheses of antifungals containing the novel pharmacophores: oxaziridines, sulfonyloxaziridines, nitrones and nitronyl nitroxides. We hypothesized that multiple copies of the pharmacophore per molecule might be a prerequisite to enhance efficacy against the opportunistic pathogen, Pneumocystis carinii. Therefore structural optimization of the leads was based on this new “multivalency” approach. All bisoxaziridines were inactive, but a trisoxaziridine caused ca. 50% reduction of the number of P. carinii tropozoites, compared to TMP-SMX, and a hexaoxaziridine at 1 µg/ml showed activity comparable to the currently used drug, TMP-SMX. Insertion of three units of the nitronyl nitroxide pharmacophore per molecule afforded …

Calcium Binding To Calmodulin Mutants Monitored By Domain-Specific Intrinsic Phenylalanine And Tyrosine Fluorescence, W. S. Vanscyoc, B. R. Sorensen, E. Rusinova, William Laws, J. B. A. Ross, M. A. Shea

Chemistry and Biochemistry Faculty Publications

Cooperative calcium binding to the two homologous domains of calmodulin (CaM) induces conformational changes that regulate its association with and activation of numerous cellular target proteins. Calcium binding to the pair of high-affinity sites (III and IV in the C-domain) can be monitored by observing calcium-dependent changes in intrinsic tyrosine fluorescence intensity (lambda(ex)/lambda(em) of 277/320 nm). However, calcium binding to the low-affinity sites (I and II in the N-domain) is more difficult to measure with optical spectroscopy because that domain of CaM does not contain tryptophan or tyrosine. We recently demonstrated that calcium-dependent changes in intrinsic phenylalanine fluorescence (lambdaex/lambdaem of …

Anisomycin Activates Jnk And Sensitises Du 145 Prostate Carcinoma Cells To Fas Mediated Apoptosis, James Curtin, Thomas Cotter

Articles

Treatment of the hormone refractory prostate cancer cell line DU 145 with sublethal concentrations of chemotherapeutic drugs has been reported to sensitise these cells to Fas mediated apoptosis. However, the mechanism by which this occurs has not been determined. Our group has shown that inhibition of JNK activity completely abrogates the effects of chemotherapeutic drugs. Using anisomycin, a potent JNK agonist, we have demonstrated a role for JNK in Fas mediated apoptosis in DU 145 cells. Inhibition of Caspase 8 and Caspase 9 completely inhibits this process which suggests that DU 145 cells require mitochondrial amplification of the Fas apoptotic …

Reaction Mechanism, Evolutionary Analysis, And Role Of Zinc In Drosophila Methionine-R-Sulfoxide Reductase, R. Abhilash Kumar, Ahmet Koc, Ronald Cerny, Vadim N. Gladyshev

Vadim Gladyshev Publications

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 methionine-R-sulfoxide reductase (MsrB). Herein, we have identified two MsrB families that differ by the presence of zinc. Evolutionary analyses suggested that the zinc-containing MsrB proteins are prototype enzymes and that the metal was lost in certain MsrB proteins later in evolution. Zinc-containing Drosophila MsrB was further characterized. The enzyme was found to employ a catalytic Cys¹²⁴ thiolate, which directly interacted with methionine sulfoxide, resulting in methionine and a Cys¹²⁴ sulfenic …

Guanine And 7,8-Dihydro-8-Oxo-Guanine-Specific Oxidation In Dna By Chromium(V), Kent D. Sugden, Brooke Martin

Chemistry and Biochemistry Faculty Publications

The hexavalent oxidation state of chromium [Cr(VI)] is a well-established human carcinogen, although the mechanism of cancer induction is currently unknown. Intracellular reduction of Cr(VI) forms Cr(V), which is thought to play a fundamental role in the mechanism of DNA damage by this carcinogen. Two separate pathways of DNA damage, an oxidative pathway and a metal-binding pathway, have been proposed to account for the lesions observed in cell systems. We have used a model Cr(V) complex, N,N´-ethylenebis(salicylidene-animato)oxochromium(V) [Cr(V)-Salen], to investigate the oxidative pathway of DNA damage and to elucidate the lesions generated from this oxidation process. Reaction of Cr(V)-Salen with …

A Comparison Of The Low Mode And Monte Carlo Conformational Search Methods, Carol A. Parish, Rosina Lombardi, Kent Sinclair, Emelyn Smith, Alla Goldberg, Melissa Rappleye, Myrianne Dure

Chemistry Faculty Publications

The Low Mode (LM) and Monte Carlo (MC) conformational search methods were compared on three diverse molecular systems; (4R, 5S, 6S, 7R)-hexahydro-5,6-dihydroxy-1,3,4,7-tetrakis(phenylmethyl)-2H-1,3-diazapin-2-one (1), 2-methoxy-2-phenyl-2-triflouromethyl-N-α-methyl benzyl propanamide (2) and a trimeric 39-membered polyazamacrolide (3). We find that either method, or a combination of the methods, is equally efficient at searching the conformational space of the smaller molecular systems while a 50:50 hybrid of Low Mode and Monte Carlo is most efficient at searching the space of the larger molecular system.

Electrically Mediated Delivery Of Vector Plasmid Dna Elicits An Antitumor Effect, L. Heller, D. Coppola

Bioelectrics Publications

In vivo electroporation is an efficient means of increasing plasmid DNA delivery to normal tissues, such as skin and muscle, as well as directly to tumors. In the experiments described here, plasmid DNA was delivered by in vivo electroporation to B16 mouse melanomas using two very different pulsing protocols. Reporter expression increased 21- or 42-fold, respectively with electroporation over injection alone. The growth of experimental melanomas with an approximate diameter of 4 mm on the day of treatment was monitored after electroporation delivery of reporter plasmid DNA. Remarkably, short-term complete regressions using one of these pulsing protocols occurred in up …

Meiotic Cohesion Requires Accumulation Of Ord On Chromosomes Before Condensation, Eric M. Balicky, Matthew W. Endres, Cary Lai, Sharon E. Bickel

Dartmouth Scholarship

Cohesion between sister chromatids is a prerequisite for accurate chromosome segregation during mitosis and meiosis. To allow chromosome condensation during prophase, the connections that hold sister chromatids together must be maintained but still permit extensive chromatin compaction. In Drosophila, null mutations in the orientation disruptor (ord) gene lead to meiotic nondisjunction in males and females because cohesion is absent by the time that sister kinetochores make stable microtubule attachments. We provide evidence that ORD is concentrated within the extrachromosomal domains of the nuclei ofDrosophila primary spermatocytes during early G2, but accumulates on the meiotic chromosomes by …

Monte Carlo Simulation On The Indirect Exchange Interactions Of Co-Doped Zno Film, Abraham F. Jalbout, Hanning Chen, Scott L. Whittenburg

Chemistry and Biochemistry Faculty Publications

Monte Carlo simulations using a three-dimensional lattice model studied the Ruderman–Kittel–Kasuya–Yosida (RKKY) indirect exchange interaction of doped magnetic Co ions in ZnOfilms. The results of the calculations show that the RKKY interaction in Co-doped ZnO is long ranged and its magnitude is proportional to (inverse of the distance from a central ion). The sign oscillates with a frequency that depends on the concentration of the carrier. The long-distance sum of the RKKY indirect exchange energies is positive indicating that these materials are ferromagnetic, in direct correlation with previously reported results.

The Atp:Co(I)Rrinoid Adenosyltransferase (Coba) Enzyme Of Salmonella Enterica Requires The 2'-Oh Group Of Atp For Function And Yields Inorganic Triphosphate As Its Reaction Byproduct, Maris V. Fonseca, Nicole R. Buan, Alexander R. Horswill, Ivan Rayment, Jorge C. Escalante-Semerena

Department of Biochemistry: Faculty Publications

The specificity of the ATP:corrinoid adenosyltransferase (CobA) enzyme of Salmonella enterica serovar Typhimurium LT2 for its nucleotide substrate was tested using ATP analogs and alternative nucleotide donors. The enzyme showed broad specificity for the nucleotide base and required the 2’-OH group of the ribosyl moiety of ATP for activity. ³¹P NMR spectroscopy was used to identify inorganic triphosphate (PPP_i) as the byproduct of the reaction catalyzed by the CobA enzyme. Cleavage of triphosphate into pyrophosphate and orthophosphate did not occur, indicating that triphosphate cleavage was not required for release of the adenosylcorrinoid product. Triphosphate was a strong …

Inhibition Of Prostate Tumor Cell Hyaluronan Synthesis Impairs Subcutaneous Growth And Vascularization In Immunocompromised Mice, Melanie A. Simpson, Christopher M. Wilson, James B. Mccarthy

Department of Biochemistry: Faculty Publications

Hyaluronan (HA), a secreted glycosaminoglycan component of extracellular matrices, is critical for cellular proliferation and motility during development. However, elevated circulating and cell-associated levels correlate with various types of cancer, including prostate. We have previously shown that aggressive PC3M-LN4 prostate tumor cells synthesize excessive HA relative to less aggressive cells, and express correspondingly higher levels of the HA biosynthetic enzymes HAS2 and HAS3. Inhibition of these enzymes by stable transfection of PC3M-LN4 cells with anti-sense HAS2 or HAS3 expression constructs diminishes HA synthesis and surface retention. In this report, we used these HA-deficient cell lines to examine the role of …

Kalirin Dbl-Homology Guanine Nucleotide Exchange Factor 1 Domain Initiates New Axon Outgrowths Via Rhog-Mediated Mechanisms, Victor May, Martin R. Schiller, Betty A. Eipper, Richard E. Mains

Life Sciences Faculty Research

The large multidomain Kalirin and Trio proteins containing dual Rho GTPase guanine nucleotide exchange factor (GEF) domains have been implicated in the regulation of neuronal fiber extension and pathfinding during evelopment. In mammals, Kalirin is expressed predominantly in the nervous system, whereas Trio, broadly expressed throughout the body, is expressed at a lower level in the nervous system. To evaluate the role of Kalirin in fiber initiation and outgrowth, we microinjected cultured sympathetic neurons with vectors encoding Kalirin or with Kalirin antisense oligonucleotides, and we assessed neuronal fiber growth in a serum-free, satellite cell-free environment. Kalirin antisense oligonucleotides blocked the …

Glutathione Levels And Bax Activation During Apoptosis Due To Oxidative Stress In Cells Expressing Wild-Type And Mutant Cystic Fibrosis Transmembrane Conductance Regulator, Thomas Jungas, Iris Motta, Francis Duffieux, Pascale Fanen, Veronique Stoven, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Cystic fibrosis is characterized by chronic inflammation and an imbalance in the concentrations of alveolar and lung oxidants and antioxidants, which result in cell damage. Modifications in lung glutathione concentrations are recognized as a salient feature of inflammatory lung diseases such as cystic fibrosis, and glutathione plays a major role in protection against oxidative stress and is important in modulation of apoptosis. The cystic fibrosis transmembrane conductance regulator (CFTR) is permeable to Cl−, larger organic ions, and reduced and oxidized forms of glutathione, and the ΔF508 CFTR mutation found in cystic fibrosis patients has been correlated with impaired glutathione transport …

Selenoproteins And Selenocysteine Insertion System In The Model Plant Cell System, Chlamydomonas Reinhardtii, Sergey V. Novoselov, Mahadev Rao, Natalia V. Onoshko, Huijun Zhi, Gregory V. Kryukov, Youbin Xiang, Donald P. Weeks, Dolph A. Hatfield, Vadim Gladyshev

Vadim Gladyshev Publications

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 the plant kingdom, Chlumydomonas reinhardtii, and directly identified two of them as phospholipid hydroperoxide glutathione peroxidase and selenoprotein W homologs. Moreover, a selenocysteyl-tRNA was isolated that recognized specifically the Sec codon UGA. Subsequent gene cloning and bioinformatics analyses identified eight additional selenoproteins, including methionine-Ssulfoxide reductase, a selenoprotein specific to Chlumydomonas. Chlumydomonas selenoprotein genes contained selenocysteine insertion sequence (SECIS) elements that were similar, but not identical, to those of animals. These SECIS elements could direct …