Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.16.3.1 (ceruloplasmin)
5,074 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible potentiation of an infection upon the metabolic consequences of trauma was tested in rats using a 2 X 2 block design which included control, femoral fracture, pneumococcal infection, and fracture plus infection groups. Infection introduced unique metabolic effects different from those of starvation, femoral fracture, or both together. Infection-induced effects included an accelerated conversion of 14C-alanine to glucose, higher serum haptoglobin, alpha2-macrofetoprotein, copper, and ceruloplasmin values, and lower serum iron, zinc, and transferrin concentrations. The first three of these infection-induced effects were diminished in rats with a femoral fracture. No measured effect of infection was increased in traumatized rats.
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PMID:Specific metabolic effects imposed by Streptococcus pneumoniae upon the response to femoral fracture in the rat. 90 63

Iron is an essential nutrient for nearly all organisms but presents problems of toxicity, poor solubility and low availability. These problems are alleviated through the use of iron-storage proteins. Bacteria possess two types of iron-storage protein, the haem-containing bacterioferritins and the haem-free ferritins. These proteins are widespread in bacteria, with at least 39 examples known so far in eubacteria and archaebacteria. The bacterioferritins and ferritins are distantly related but retain similar structural and functional properties. Both are composed of 24 identical or similar subunits (approximately 19 kDa) that form a roughly spherical protein (approximately 450 kDa, approximately 120 A diameter) containing a large hollow centre (approximately 80 A diameter). The hollow centre acts as an iron-storage cavity with the capacity to accommodate at least 2000 iron atoms in the form of a ferric-hydroxyphosphate core. Each subunit contains a four-helix bundle which carries the active site or ferroxidase centre of the protein. The ferroxidase centres endow ferrous-iron-oxidizing activity and are able to form a di-iron species that is an intermediate in the iron uptake, oxidation and core formation process. Bacterioferritins contain up to 12 protoporphyrin IX haem groups located at the two-fold interfaces between pairs of two-fold related subunits. The role of the haem is unknown, although it may be involved in mediating iron-core reduction and iron release. Some bacterioferritins are composed of two subunit types, one conferring haem-binding ability (alpha) and the other (beta) bestowing ferroxidase activity. Bacterioferritin genes are often adjacent to genes encoding a small [2Fe-2S]-ferredoxin (bacterioferritin-associated ferredoxin or Bfd). Bfd may directly interact with bacterioferritin and could be involved in releasing iron from (or delivering iron to) bacterioferritin or other iron complexes. Some bacteria contain two bacterioferritin subunits, or two ferritin subunits, that in most cases co-assemble. Others possess both a bacterioferritin and a ferritin, while some appear to lack any type of iron-storage protein. The reason for these differences is not understood. Studies on ferritin mutants have shown that ferritin enhances growth during iron starvation and is also involved in iron accumulation in the stationary phase of growth. The ferritin of Campylobacter jejuni is involved in redox stress resistance, although this does not appear to be the case for Escherichia coli ferritin (FtnA). No phenotype has been determined for E. coli bacterioferritin mutants and the precise role of bacterioferritin in E. coli remains uncertain.
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PMID:Iron storage in bacteria. 988 81

Ferritins managing iron-oxygen biochemistry in animals, plants, and microorganisms belong to the diiron carboxylate protein family and concentrate iron as ferric oxide approximately 10(14) times above the ferric K(s). Ferritin iron (up to 4,500 atoms), used for iron cofactors and heme, or to trap DNA-damaging oxidants in microorganisms, is concentrated in the protein nanocage cavity (5-8 nm) formed during assembly of polypeptide subunits, 24 in maxiferritins and 12 in miniferritins/DNA protection during starvation proteins. Direct identification of ferritin ferroxidase (F(ox)) sites, complicated by multiple types of iron-ferritin interactions, is now achieved with chimeric proteins where putative F(ox) site residues were introduced singly and cumulatively into an inactive host, an L maxiferritin. A dimagnesium ferritin cocrystal model guided site design and the diferric peroxo F(ox) intermediates (A at 650 nm) monitored activity. Diferric peroxo formation in chimeric and WT proteins had similar K(app) values and Hill coefficients. Catalytic activity required cooperative ferrous substrate binding to two sites A (E, EXXH) and B (E, QXXD). The weaker B sites in ferritin contrast with stronger B sites (E, EXXH) in diiron carboxylate oxygenases, explaining diferric oxo/hydroxo product release in ferritin vs. diiron cofactor retention in oxygenases. Codons for Q/H and D/E differ by single nucleotides, suggesting simple DNA mutations relate site B diiron substrate sites and diiron cofactor sites in proteins. The smaller k(cat) values in chimeras indicate the absence of second-shell residues important for ferritin substrate-product channeling that, when identified, will outline the entire iron path from ferritin pores through the F(ox) site to the mineral cavity.
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PMID:Ferritin reactions: direct identification of the site for the diferric peroxide reaction intermediate. 1516 87

The crystal structure of the Dps-like (Dps, DNA-protecting protein during starvation) ferritin protein DpsA from the halophile Halobacterium salinarum was determined with low endogenous iron content at 1.6-A resolution. The mechanism of iron uptake and storage was analyzed in this noncanonical ferritin by three high-resolution structures at successively increasing iron contents. In the high-iron state of the DpsA protein, up to 110 iron atoms were localized in the dodecameric protein complex. For ultimate iron storage, the archaeal ferritin shell comprises iron-binding sites for iron translocation, oxidation, and nucleation. Initial iron-protein interactions occur through acidic residues exposed along the outer surface in proximity to the iron entry pore. This narrow pore permits translocation of ions toward the ferroxidase centers via two discrete steps. Iron oxidation proceeds by transient formation of tri-iron ferroxidase centers. Iron storage by biomineralization inside the ferritin shell occurs at two iron nucleation centers. Here, a single iron atom provides a structural seed for iron-oxide cluster formation. The clusters with up to five iron atoms adopt a geometry that is different from natural biominerals like magnetite but resembles iron clusters so far known only from bioinorganic model compounds.
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PMID:Iron-oxo clusters biomineralizing on protein surfaces: structural analysis of Halobacterium salinarum DpsA in its low- and high-iron states. 1536 82

The main purpose of this article is to review the previously published data on so-called "moose sickness" in the light of two case studies presented here. Molybdenosis and Mo-induced disturbances of Cu metabolism in moose are characterized by numerous severe lesions caused by reduced activity of Cu-containing enzymes such as ceruloplasmin, superoxide dismutase in blood, and myocardial cytochrome c oxidase. Consequences of such metabolic disturbances (e.g. glucose intolerance, insulin resistance, and non-insulin-dependent diabetes mellitus) were first reported in moose in 2000. This was corroborated by the detection of furosine, pentosidine, and Nepsilon-(carboxymethyl)-lysine in blood plasma and the kidney, indicating long-term hyperglycemia. Increased concentrations of insulin, glucose, and urea and reduced levels of phosphate, T4, and Mg in blood were also seen. Recently, a similar toxic endocrinopathy was reported in sheep treated therapeutically with thiomolybdates because of chronic Cu toxicosis. Two case reports illustrate the difficulty of diagnosing Mo-related disturbances of Cu metabolism in moose, as analyses of Cu and Mo have not proved entirely reliable because of interaction, accumulation, and the short biological half-life of Mo. The increased bioavailability of Mo is most probably the result of increased pH in the soil, caused, for example, by liming, making Mo accessible in forage plants consumed by moose. The etiology underlying the Swedish moose disease has been difficult to determine because of the complex clinical signs and unspecific pathological findings. However, a combination of clinical chemistry, trace element analysis, and biochemistry correlated with the pathological findings has corroborated molybdenosis and Mo-induced disturbances of Cu metabolism as the probable etiological factor. Alternative etiologies suggested for the moose disease, such as viral infection, starvation because of overpopulation, and/or shortage of forage as well as senescence and phytotoxic substances, are discussed.
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PMID:A review of the "mysterious" wasting disease in Swedish moose (Alces alces L.) related to molybdenosis and disturbances in copper metabolism. 1562 35

Bacterial iron storage proteins such as ferritin serve as intracellular iron reserves. Members of the DNA protection during starvation (Dps) family of proteins are structurally related to ferritins, and their function is to protect the genome from iron-induced free radical damage. Some members of the Dps family bind DNA and are thought to do so only as fully assembled dodecamers. We present the cloning and characterization of a Dps homolog encoded by the radiation-resistant eubacterium Deinococcus radiodurans and show that DNA binding does not require its assembly into a dodecamer. D.radiodurans Dps-1, the product of gene DR2263, adopts a stably folded conformation, as demonstrated by circular dichroism spectroscopy, and undergoes a transition to a disordered state with a melting temperature of 69.2(+/-0.1) degrees C. While a dimeric form of Dps-1 is observed under low-salt conditions, a dodecameric assembly is highly favored at higher concentrations of salt. Both oligomeric forms of Dps-1 exhibit ferroxidase activity, and Fe(II) oxidation/mineralization is seen for dodecameric Dps-1. Notably, addition of Ca(2+) (to millimolar concentrations) to dodecameric Dps-1 can result in the reduction of bound Fe(III). Dimeric Dps-1 protects DNA from both hydroxyl radical cleavage and from DNase I-mediated cleavage; however, dodecameric Dps-1 is unable to provide efficient protection against hydroxyl radical-mediated DNA cleavage. While dodecameric Dps-1 does bind DNA, resulting in formation of large aggregates, cooperative DNA binding by dimeric Dps-1 leads to formation of protein-DNA complexes of finite stoichiometry.
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PMID:Differential DNA binding and protection by dimeric and dodecameric forms of the ferritin homolog Dps from Deinococcus radiodurans. 1575 46

Genes whose expression levels are enhanced or reduced during the cultivation process that uses cane molasses in baker's yeast production were identified in this study. The results showed that baker's yeast grown in molasses medium had higher fermentation ability and stress tolerance compared with baker's yeast grown in synthetic medium. Molasses apparently provided not only sugar as a carbon source but also provided functional components that enhanced or reduced expression of genes involved in fermentation ability and stress tolerance. To identify the genes whose expression is enhanced or reduced during cultivation in molasses medium, DNA microarray analysis was then used to compare the gene expression profile of cells grown in molasses with that of cells grown in synthetic medium. To simulate the commercial baker's yeast production process, cells were cultivated using a fed-batch culture system. In molasses medium, genes involved in the synthesis or uptake of vitamins (e.g., biotin, pyridoxine and thiamine) showed enhanced expression, suggesting that vitamin concentrations in molasses medium were lower than those in synthetic medium. Genes involved in formate dehydrogenase and maltose assimilation showed enhanced expression in molasses medium. In contrast, genes involved in iron utilization (e.g., siderophore, iron transporter and ferroxidase) showed enhanced expression in synthetic medium, suggesting that iron starvation occurred. The genes involved in the metabolism of amino acids also showed enhanced expression in synthetic medium. This identification of genes provides information that will help improve the baker's yeast production process.
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PMID:Identification of genes whose expressions are enhanced or reduced in baker's yeast during fed-batch culture process using molasses medium by DNA microarray analysis. 1592 3

DNA protection during starvation (Dps) proteins play an important role in protecting cellular macromolecules from damage by reactive oxygen species (ROS). Unlike most orthologs that protect DNA by a combination of DNA binding and prevention of hydroxyl radical formation by ferroxidation and sequestration of iron, Dps-1 from the radiation-resistant Deinococcus radiodurans fails to protect DNA from hydroxyl radical-mediated cleavage through a mechanism inferred to involve continuous release of iron from the protein core. To address the structural basis for this unusual release of Fe(2+), the crystal structure of D. radiodurans Dps-1 was determined to 2.0 Angstroms resolution. Two of four strong anomalous signals per protein subunit correspond to metal-binding sites within an iron-uptake channel and a ferroxidase site, common features related to the canonical functions of Dps homologs. Similar to Lactobacillus lactis Dps, a metal-binding site is found at the N-terminal region. Unlike other metal sites, this site is located at the base of an N-terminal coil on the outer surface of the dodecameric protein sphere and does not involve symmetric association of protein subunits. Intriguingly, a unique channel-like structure is seen featuring a fourth metal coordination site that results from 3-fold symmetrical association of protein subunits through alpha2 helices. The presence of this metal-binding site suggests that it may define an iron-exit channel responsible for the continuous release of iron from the protein core. This interpretation is supported by substitution of residues involved in this ion coordination and the observation that the resultant mutant protein exhibits significantly attenuated iron release. Therefore, we propose that D. radiodurans Dps-1 has a distinct iron-exit channel.
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PMID:Crystal structure of Dps-1, a functionally distinct Dps protein from Deinococcus radiodurans. 1682 1

Dps (DNA protection during starvation) proteins, mini-ferritins in the ferritin superfamily, catalyze Fe(2+)/H(2)O(2)/O(2) reactions and make minerals inside protein nanocages to minimize radical oxygen-chemistry (metal/osmotic/temperature/nutrient/oxidant) and sometimes to confer virulence. Paired Dps proteins in Bacillus, rare in other bacteria, have 60% sequence identity. To explore functional differences in paired Bacilli Dps protein, we measured ferroxidase activity and DNA protection (hydroxyl radical) for Dps protein dodecamers from Bacillus anthracis (Ba) since crystal structures and iron mineralization (iron-stain) were known. The self-assembled (200 kDa) Ba Dps1 (Dlp-1) and Ba Dps2 (Dlp-2) proteins had similar Fe(2+)/O(2) kinetics, with space for minerals of 500 iron atoms/protein, and protected DNA. The reactions with Fe(2+) were novel in several ways: 1) Ba Dps2 reactions (Fe(2+)/H(2)O(2)) proceeded via an A(650 nm) intermediate, with similar rates to maxi-ferritins (Fe(2+)/O(2)), indicating a new Dps protein reaction pathway, 2) Ba Dps2 reactions (Fe(2+)/O(2) versus Fe(2+)/O(2) + H(2)O(2)) differed 3-fold contrasting with Escherichia coli Dps reactions, with 100-fold differences, and 3) Ba Dps1, inert in Fe(2+)/H(2)O(2) catalysis, inhibited protein-independent Fe(2+)/H(2)O(2) reactions. Sequence similarities between Ba Dps1 and Bacillus subtilis DpsA (Dps1), which is regulated by general stress factor (SigmaB) and Fur, and between Ba Dps2 and B. subtilis MrgA, which is regulated by H(2)O(2) (PerR), suggest the function of Ba Dps1 is iron sequestration and the function of Ba Dps2 is H(2)O(2) destruction, important in host/pathogen interactions. Destruction of H(2)O(2) by Ba Dps2 proceeds via an unknown mechanism with an intermediate similar spectrally (A(650 nm)) and kinetically to the maxi-ferritin diferric peroxo complex.
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PMID:Paired Bacillus anthracis Dps (mini-ferritin) have different reactivities with peroxide. 1686 Dec 27

Dps (DNA protection during starvation) is a member of the iron-binding protein family in prokaryotes. It has been shown previously that Dps possesses ferroxidase activity and the ability to sequester iron that seems to protect DNA from oxidative damage. Based on the method of Polymerase Chain Reaction and homologous genetic recombination in vivo, the gene (DRB0092) encoding a Dps protein homology in the extremely radioresistant bacterium Deinococcus radiodurans was deleted from the wild type strain R1 genome. The obtained mutant was designated as Kdps and further verified by PCR and sequencing. Survival rates of the mutant and wild type strain were investigated after challenged with different doses of hydrogen peroxide (H2O2). Results showed that the survival rate of dps mutant reduced rapidly under the low concentration of H2O2 (< or = 10mmol/L), while the wild type strain showed no sudden decrease. When the H2O2 concentration was higher than 30mmol/L, the difference of the survival rates between the mutant and wild type was more than 50-folds. The result demonstrated that the loss of dps gene in D. radiodurans made cells become more sensitive to oxidative damage. An iron staining method was used to determinate catalase activity in native polyacrylamide electrophoresis gels. The result displayed that two catalases in dps mutant were enhanced about 2-folds than that of wild type. The soluble Dps protein was obtained after construction of expression plasmid and inducement in E. coli transformant. The Dps protein showed the capacity of DNA binding and protected DNA from hydroxyl free radical cleavage in vitro. This study demonstrates that Dps protein of D. radiodurans plays an important role in its antioxidant system, which may contribute to its extreme resistance of this bacterium.
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PMID:[Construction of a dps mutant and its functional analysis in Deinococcus radiodurans]. 1794 59


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