Methionine Sulfoxide Reductases: Reductases that catalyze the reaction of peptide-L-methionine -S-oxide + thioredoxin to produce peptide-L-methionine + thioredoxin disulfide + H(2)O.Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)Sulfenic Acids: Oxy acids of sulfur with the general formula RSOH, where R is an alkyl or aryl group such as CH3. They are often encountered as esters and halides. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.Thioredoxins: Hydrogen-donating proteins that participates in a variety of biochemical reactions including ribonucleotide reduction and reduction of PEROXIREDOXINS. Thioredoxin is oxidized from a dithiol to a disulfide when acting as a reducing cofactor. The disulfide form is then reduced by NADPH in a reaction catalyzed by THIOREDOXIN REDUCTASE.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Selenoproteins: Selenoproteins are proteins that specifically incorporate SELENOCYSTEINE into their amino acid chain. Most selenoproteins are enzymes with the selenocysteine residues being responsible for their catalytic functions.Thioredoxin-Disulfide Reductase: A FLAVOPROTEIN enzyme that catalyzes the oxidation of THIOREDOXINS to thioredoxin disulfide in the presence of NADP+. It was formerly listed as EC 220.127.116.11Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Glutaredoxins: A family of thioltransferases that contain two active site CYSTEINE residues, which either form a disulfide (oxidized form) or a dithiol (reduced form). They function as an electron carrier in the GLUTHIONE-dependent synthesis of deoxyribonucleotides by RIBONUCLEOTIDE REDUCTASES and may play a role in the deglutathionylation of protein thiols. The oxidized forms of glutaredoxins are directly reduced by the GLUTATHIONE.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Paraquat: A poisonous dipyridilium compound used as contact herbicide. Contact with concentrated solutions causes irritation of the skin, cracking and shedding of the nails, and delayed healing of cuts and wounds.Selenocysteine: A naturally occurring amino acid in both eukaryotic and prokaryotic organisms. It is found in tRNAs and in the catalytic site of some enzymes. The genes for glutathione peroxidase and formate dehydrogenase contain the TGA codon, which codes for this amino acid.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Sulfoxides: Organic compounds that have the general formula R-SO-R. They are obtained by oxidation of mercaptans (analogous to the ketones). (From Hackh's Chemical Dictionary, 4th ed)Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Iron-Sulfur Proteins: A group of proteins possessing only the iron-sulfur complex as the prosthetic group. These proteins participate in all major pathways of electron transport: photosynthesis, respiration, hydroxylation and bacterial hydrogen and nitrogen fixation.Oxidants: Electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (OXIDATION-REDUCTION).Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. PLASTID GENOMES are used in phylogenetic studies.Sulfhydryl Compounds: Compounds containing the -SH radical.Neisseria meningitidis: A species of gram-negative, aerobic BACTERIA. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the NASOPHARYNX. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis (MENINGITIS, MENINGOCOCCAL). It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being A, B, C, Y, and W-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Disulfides: Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Bacterial Proteins: Proteins found in any species of bacterium.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Methionine sulfoxideMethionineGlucose-methanol-choline oxidoreductase family: In molecular biology, the glucose-methanol-choline oxidoreductase family (GMC oxidoreductase) is a family of enzymes with oxidoreductase activity.Sulfenic acidDimethyl sulfoxideFerredoxin-thioredoxin reductase: Ferredoxin-thioredoxin reductase , systematic name ferredoxin:thioredoxin disulfide oxidoreductase, is a [4Fe-4S] protein that plays an important role in the ferredoxin/thioredoxin regulatory chain. It catalyzes the following reaction:Table of standard reduction potentials for half-reactions important in biochemistry: The values below are standard reduction potentials for half-reactions measured at 25°C, 1 atmosphere and a pH of 7 in aqueous solution.Selenoprotein: In molecular biology a selenoprotein is any protein that includes a selenocysteine (Sec, U, Se-Cys) amino acid residue. Among functionally characterized selenoproteins are five glutathione peroxidases (GPX) and three thioredoxin reductases, (TrxR/TXNRD) which both contain only one Sec.Thioredoxin reductaseVaporized hydrogen peroxide: Vaporized hydrogen peroxide — also known as hydrogen peroxide vapor, HPV, and by the trademarked name VHP — is a vapor form of hydrogen peroxide (H2O2) with applications as a low-temperature antimicrobial vapor used to decontaminate enclosed and sealed areas such as laboratory workstations, isolation and pass-through rooms, and even aircraft interiors.Coles PhillipsGlutaredoxin 2 (bacterial): In molecular biology, the glutaredoxin 2 family is a family of bacterial glutaredoxins. Unlike other glutaredoxins, glutaredoxin 2 (Grx2) cannot reduce ribonucleotide reductase.Acid catalysis: In acid catalysis and base catalysis a chemical reaction is catalyzed by an acid or a base. The acid is the proton donor and the base is the proton acceptor.Protein primary structure: The primary structure of a peptide or protein is the linear sequence of its amino acid structural units, and partly comprises its overall biomolecular structure. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end.Paraquat murders: The paraquat murders were a series of indiscriminate poisonings carried out in Japan in 1985. Police were unable to gather any evidence about the murders other than they were caused by a poisoned beverage that was left inside or around vending machines.SECIS elementList of strains of Escherichia coli: Escherichia coli is a well studied bacterium that was first identified by Theodor Escherich, after whom it was later named.Sharpless asymmetric dihydroxylation: Sharpless asymmetric dihydroxylation (also called the Sharpless bishydroxylation) is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol.SulfoxideIron-sulfur cluster biosynthesis protein family: In molecular biology, the iron-sulfur cluster biosynthesis protein family of includes proteins involved in biogenesis of Fe-S clusters (iron-sulfur cluster insertion protein, Fe/S biogenesis protein). This family includes IscA, HesB, YadR and YfhF-like proteins.Stromule: A stromule is a microscopic structure found in plant cells. Stromules (stroma-filled tubules) are highly dynamic structures extending from the surface of all plastid types, including proplastids, chloroplasts, etioplasts, leucoplasts, amyloplasts, and chromoplasts.Perchloromethyl mercaptanNeisseria meningitidis: Neisseria meningitidis, often referred to as meningococcus, is a gram negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to as a coccus because it is round, and more specifically, diplococcus because of its tendency to form pairs.DsbC protein family: DsbC (Disulfide bond C) is a prokaryotic disulfide bond isomerase. The formation of native disulfide bonds play an important role in the proper folding of proteins and stabilize tertiary structures of the protein.Ferric uptake regulator family: In molecular biology, the ferric uptake regulator (FUR) family of proteins includes metal ion uptake regulator proteins. These are responsible for controlling the intracellular concentration of iron in many bacteria.Symmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.
(1/224) Identification of a second major tumor-specific antigen recognized by CTLs on mouse mastocytoma P815.
Murine mastocytoma P815 induces CTL responses against at least four distinct Ags (AB, C, D, and E). Recent studies have shown that the main component of the CTL response against the P815 tumor is targeted against Ags P815AB and P815E. The gene P1A has been well characterized. It encodes the P815AB Ag in the form of a nonameric peptide containing two epitopes, P815A and P815B, which are recognized by different CTLs. Here, we report the identification of the P815E Ag. Using a cDNA library derived from tumor P815, we identified the gene coding for P815E. We also characterized the antigenic peptide that anti-P815E CTLs recognize on the MHC class I molecule H-2Kd. The P815E Ag results from a mutation within an ubiquitously expressed gene encoding methionine sulfoxide reductase, an enzyme that is believed to be important in the protection of proteins against the by-products of aerobic metabolism. Surprisingly, immunizing mice i.p. with syngeneic tumor cells (L1210) that were constructed to express B7-1 and P815E did not induce resistance against live P815, even though a strong anti-P815E CTL response was observed with splenocytes from immunized animals. (+info)
(2/224) Diastereoselective reduction of protein-bound methionine sulfoxide by methionine sulfoxide reductase.
Methionine sulfoxide (MetSO) in calmodulin (CaM) was previously shown to be a substrate for bovine liver peptide methionine sulfoxide reductase (pMSR, EC 18.104.22.168), which can partially recover protein structure and function of oxidized CaM in vitro. Here, we report for the first time that pMSR selectively reduces the D-sulfoxide diastereomer of CaM-bound L-MetSO (L-Met-D-SO). After exhaustive reduction by pMSR, the ratio of L-Met-D-SO to L-Met-L-SO decreased to about 1:25 for hydrogen peroxide-oxidized CaM, and to about 1:10 for free MetSO. The accumulation of MetSO upon oxidative stress and aging in vivo may be related to incomplete, diastereoselective, repair by pMSR. (+info)
(3/224) Molecular cloning and functional expression of a human peptide methionine sulfoxide reductase (hMsrA).
Oxidation of methionine residues in proteins to methionine sulfoxide can be reversed by the enzyme peptide methionine sulfoxide reductase (MsrA, EC 22.214.171.124). We cloned the gene encoding a human homologue (hMsrA) of the enzyme, which has an 88% amino acid sequence identity to the bovine version (bMsrA). With dot blot analyses based on RNA from human tissues, expression of hMsrA was found in all tissues tested, with highest mRNA levels in adult kidney and cerebellum, followed by liver, heart ventricles, bone marrow and hippocampus. In fetal tissue, expression was highest in the liver. No expression of hmsrA was detected in leukemia and lymphoma cell lines. To test if hMsrA is functional in cells, we assayed its effect on the inactivation time course of the A-type potassium channel ShC/B since this channel property strongly depends on the oxidative state of a methionine residue in the N-terminal part of the polypeptide. Co-expression of ShC/B and hMsrA in Xenopus oocytes significantly accelerated inactivation, showing that the cloned enzyme is functional in an in vivo assay system. Furthermore, the activity of a purified glutathione-S-transferase-hMsrA fusion protein was demonstrated in vitro by measuring the reduction of [3H]N-acetyl methionine sulfoxide. (+info)
(4/224) Inactivation of MXR1 abolishes formation of dimethyl sulfide from dimethyl sulfoxide in Saccharomyces cerevisiae.
Dimethyl sulfide (DMS) is a sulfur compound of importance for the organoleptic properties of beer, especially some lager beers. Synthesis of DMS during beer production occurs partly during wort production and partly during fermentation. Methionine sulfoxide reductases are the enzymes responsible for reduction of oxidized cellular methionines. These enzymes have been suggested to be able to reduce dimethyl sulfoxide (DMSO) as well, with DMS as the product. A gene for an enzymatic activity leading to methionine sulfoxide reduction in Saccharomyces yeast was recently identified. We confirmed that the Saccharomyces cerevisiae open reading frame YER042w appears to encode a methionine sulfoxide reductase, and propose the name MXR1 for the gene. We found that Mxr1p catalyzes reduction of DMSO to DMS and that an mxr1 disruption mutant cannot reduce DMSO to DMS. Mutant strains appear to have unchanged fitness under several laboratory conditions, and in this paper I hypothesize that disruption of MXR1 in brewing yeasts would neutralize the contribution of the yeast to the DMS content in beer. (+info)
(5/224) New mammalian selenocysteine-containing proteins identified with an algorithm that searches for selenocysteine insertion sequence elements.
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 3'-untranslated regions of selenoprotein genes contain a common stem-loop structure, selenocysteine insertion sequence (SECIS) element, that is necessary for decoding UGA as selenocysteine rather than a stop signal. We describe here a computer program, SECISearch, that identifies mammalian selenoprotein genes by recognizing SECIS elements on the basis of their primary and secondary structures and free energy requirements. When SECISearch was applied to search human dbEST, two new mammalian selenoproteins, designated SelT and SelR, were identified. We determined their cDNA sequences and expressed them in a monkey cell line as fusion proteins with a green fluorescent protein. Incorporation of selenium into new proteins was confirmed by metabolic labeling with (75)Se, and expression of SelT was additionally documented in immunoblot assays. SelT and SelR did not have homology to previously characterized proteins, but their putative homologs were detected in various organisms. SelR homologs were present in every organism characterized by complete genome sequencing. The data suggest applicability of SECISearch for identification of new selenoprotein genes in nucleotide data bases. (+info)
(6/224) Reactive oxygen species and nitric oxide mediate plasticity of neuronal calcium signaling.
Reactive oxygen species (ROS) and nitric oxide (NO) are important participants in signal transduction that could provide the cellular basis for activity-dependent regulation of neuronal excitability. In young rat cortical brain slices and undifferentiated PC12 cells, paired application of depolarization/agonist stimulation and oxidation induces long-lasting potentiation of subsequent Ca(2+) signaling that is reversed by hypoxia. This potentiation critically depends on NO production and involves cellular ROS utilization. The ability to develop the Ca(2+) signal potentiation is regulated by the developmental stage of nerve tissue, decreasing markedly in adult rat cortical neurons and differentiated PC12 cells. (+info)
(7/224) HIV-2 protease is inactivated after oxidation at the dimer interface and activity can be partly restored with methionine sulphoxide reductase.
Human immunodeficiency viruses encode a homodimeric protease that is essential for the production of infectious virus. Previous studies have shown that HIV-1 protease is susceptible to oxidative inactivation at the dimer interface at Cys-95, a process that can be reversed both chemically and enzymically. Here we demonstrate a related yet distinct mechanism of reversible inactivation of the HIV-2 protease. Exposure of the HIV-2 protease to H(2)O(2) resulted in conversion of the two methionine residues (Met-76 and Met-95) to methionine sulphoxide as determined by amino acid analysis and mass spectrometry. This oxidation completely inactivated protease activity. However, the activity could be restored (up to 40%) after exposure of the oxidized protease to methionine sulphoxide reductase. This treatment resulted in the reduction of methionine sulphoxide 95 but not methionine sulphoxide 76 to methionine, as determined by peptide mapping/mass spectrometry. We also found that exposure of immature HIV-2 particles to H(2)O(2) led to the inhibition of polyprotein processing in maturing virus particles comparable to that demonstrated for HIV-1 particles. Thus oxidative inactivation of the HIV protease in vitro and in maturing viral particles is not restricted to the type 1 proteases. These studies indicate that two distinct retroviral proteases are susceptible to inactivation after a very minor modification at residue 95 of the dimer interface and suggest that the dimer interface might be a viable target for the development of novel protease inhibitors. (+info)
(8/224) Expression of UGA-containing Mycoplasma genes in Bacillus subtilis.
We used Bacillus subtilis to express UGA-containing Mycoplasma genes encoding the P30 adhesin (one UGA) of Mycoplasma pneumoniae and methionine sulfoxide reductase (two UGAs) of Mycoplasma genitalium. Due to natural UGA suppression, these Mycoplasma genes were expressed as full-length protein products, but at relatively low efficiency, in recombinant wild-type Bacillus. The B. subtilis-expressed Mycoplasma proteins appeared as single bands and not as multiple bands compared to expression in recombinant Escherichia coli. Bacillus mutants carrying mutations in the structural gene (prfB) for release factor 2 markedly enhanced the level of readthrough of UGA-containing Mycoplasma genes. (+info)