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  1. Article ; Online: Improving reusability along the data life cycle: a regulatory circuits case study.

    Louarn, Marine / Chatonnet, Fabrice / Garnier, Xavier / Fest, Thierry / Siegel, Anne / Faron, Catherine / Dameron, Olivier

    Journal of biomedical semantics

    2022  Volume 13, Issue 1, Page(s) 11

    Abstract: Background: In life sciences, there has been a long-standing effort of standardization and integration of reference datasets and databases. Despite these efforts, many studies data are provided using specific and non-standard formats. This hampers the ... ...

    Abstract Background: In life sciences, there has been a long-standing effort of standardization and integration of reference datasets and databases. Despite these efforts, many studies data are provided using specific and non-standard formats. This hampers the capacity to reuse the studies data in other pipelines, the capacity to reuse the pipelines results in other studies, and the capacity to enrich the data with additional information. The Regulatory Circuits project is one of the largest efforts for integrating human cell genomics data to predict tissue-specific transcription factor-genes interaction networks. In spite of its success, it exhibits the usual shortcomings limiting its update, its reuse (as a whole or partially), and its extension with new data samples. To address these limitations, the resource has previously been integrated in an RDF triplestore so that TF-gene interaction networks could be generated with two SPARQL queries. However, this triplestore did not store the computed networks and did not integrate metadata about tissues and samples, therefore limiting the reuse of this dataset. In particular, it does not enable to reuse only a portion of Regulatory Circuits if a study focuses on a subset of the tissues, nor to combine the samples described in the datasets with samples from other studies. Overall, these limitations advocate for the design of a complete, flexible and reusable representation of the Regulatory Circuits dataset based on Semantic Web technologies.
    Results: We provide a modular RDF representation of the Regulatory Circuits, called Linked Extended Regulatory Circuits (LERC). It consists in (i) descriptions of biological and experimental context mapped to the references databases, (ii) annotations about TF-gene interactions at the sample level for 808 samples, (iii) annotations about TF-gene interactions at the tissue level for 394 tissues, (iv) metadata connecting the knowledge graphs cited above. LERC is based on a modular organisation into 1,205 RDF named graphs for representing the biological data, the sample-specific and the tissue-specific networks, and the corresponding metadata. In total it contains 3,910,794,050 triples and is available as a SPARQL endpoint.
    Conclusion: The flexible and modular architecture of LERC supports biologically-relevant SPARQL queries. It allows an easy and fast querying of the resources related to the initial Regulatory Circuits datasets and facilitates its reuse in other studies. ASSOCIATED WEBSITE: https://regulatorycircuits-lod.genouest.org.
    MeSH term(s) Animals ; Biological Science Disciplines ; Databases, Factual ; Humans ; Life Cycle Stages ; Metadata
    Language English
    Publishing date 2022-03-28
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2548651-2
    ISSN 2041-1480 ; 2041-1480
    ISSN (online) 2041-1480
    ISSN 2041-1480
    DOI 10.1186/s13326-022-00266-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Anti-human immunodeficiency virus effects of zidovudine in combination with double-stranded RNA poly I poly C in T cells and monocytes-macrophages.

    Gochi, K / Sinet, M / Dazza, M C / Dameron, G / Brun-Vezinet, F

    AIDS research and human retroviruses

    1992  Volume 8, Issue 7, Page(s) 1215–1219

    Abstract: ... I poly C double-stranded RNA both alone and in combination in MT4 cells and primary monocyte/macrophage ... inhibition of reverse transcriptase production in the supernatant of M/M cultures was enhanced by the addition of poly I poly C ... that the evaluation of compounds involving the induction of an antiviral state should be tested not only CD4+ T ...

    Abstract A comparison of the activity against human immunodeficiency virus 1 of zidovudine (AZT) and poly I poly C double-stranded RNA both alone and in combination in MT4 cells and primary monocyte/macrophage (M/M) cultures was made. The inhibition of the HIV-induced cytopathic effect or reverse transcriptase production by AZT in MT4 cells was not modified by the combination of the two agents. In contrast, AZT inhibition of reverse transcriptase production in the supernatant of M/M cultures was enhanced by the addition of poly I poly C. The inhibitory effect of the drug combination was more marked in M/M than in MT4 cells, indicating that the evaluation of compounds involving the induction of an antiviral state should be tested not only CD4+ T cells but also in monocyte-macrophages.
    MeSH term(s) Cell Line ; Cell Line, Transformed ; Dose-Response Relationship, Drug ; Drug Interactions ; HIV-1/drug effects ; Humans ; Macrophages/microbiology ; Monocytes/microbiology ; Poly I-C/genetics ; Poly I-C/pharmacology ; RNA, Double-Stranded/pharmacology ; Zidovudine/pharmacology
    Chemical Substances RNA, Double-Stranded ; Zidovudine (4B9XT59T7S) ; Poly I-C (O84C90HH2L)
    Language English
    Publishing date 1992-07
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 639130-8
    ISSN 1931-8405 ; 0889-2229
    ISSN (online) 1931-8405
    ISSN 0889-2229
    DOI 10.1089/aid.1992.8.1215
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Dissecting the dimerization motif of Enterococcus hirae's Zn(II)CopY.

    Collins, Tyler C / Dameron, Charles T

    Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry

    2012  Volume 17, Issue 7, Page(s) 1063–1070

    Abstract: ... Biochemistry 41:5822-5829, 2002). Its dimerization domain contains a C-terminal cysteine-rich metal-binding ...

    Abstract The regulation of the copper homeostasis pathway in Enterococcus hirae is conducted through activity of the zinc metalloprotein Zn(II)CopY, which is a Cu(I)-responsive dimeric repressor (Cobine et al., Biochemistry 41:5822-5829, 2002). Its dimerization domain contains a C-terminal cysteine-rich metal-binding motif used for Cu(I) sensing adjacent to an aliphatic-rich repeating sequence, but it is unclear as to which regions contribute most to the interaction. To accomplish this, a synthetically produced CopY construct (CDG) was fused with solubility enhancement tags so the key components of the elements of the aliphatic repeat and metal-binding site could be probed for their dimerization activity. The resultant fusion constructs were tested using two independent methods. Isothermal titration calorimetry, an in vitro technique, was employed to determine dimer affinity thermodynamically. Protein fragment complementation, an in vivo technique, made it possible to rapidly screen homodimeric and heterodimeric complexes within live cells. The combination of in vivo and in vitro studies enabled the identification of CDG sequences that dimerize and sequences that do not, in addition to deciphering relative dimer affinity between all constructs screened. The in vivo technique allowed the formation of heterodimers to be tested for their ability to form specific complexes between dissimilar CDG analogs.
    MeSH term(s) Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Calorimetry ; Copper/chemistry ; Dimerization ; Enterococcus/enzymology ; Enterococcus/genetics ; Protein Binding ; Protein Structure, Tertiary ; Repressor Proteins/chemistry ; Repressor Proteins/genetics ; Thermodynamics ; Zinc/chemistry
    Chemical Substances Bacterial Proteins ; CopY protein, Enterococcus hirae ; Repressor Proteins ; Copper (789U1901C5) ; Zinc (J41CSQ7QDS)
    Language English
    Publishing date 2012-07-10
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1464026-0
    ISSN 1432-1327 ; 0949-8257
    ISSN (online) 1432-1327
    ISSN 0949-8257
    DOI 10.1007/s00775-012-0919-7
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Toxoplasma gondii requires its plant-like heme biosynthesis pathway for infection.

    Bergmann, Amy / Floyd, Katherine / Key, Melanie / Dameron, Carly / Rees, Kerrick C / Thornton, L Brock / Whitehead, Daniel C / Hamza, Iqbal / Dou, Zhicheng

    PLoS pathogens

    2020  Volume 16, Issue 5, Page(s) e1008499

    Abstract: ... production is essential for T. gondii intracellular growth and pathogenesis. Surprisingly, the herbicide ... oxadiazon significantly impaired Toxoplasma growth, consistent with phylogenetic analyses that show T ... biosynthesis is a druggable target. As T. gondii has been used to model other apicomplexan parasites, our study ...

    Abstract Heme, an iron-containing organic ring, is essential for virtually all living organisms by serving as a prosthetic group in proteins that function in diverse cellular activities ranging from diatomic gas transport and sensing, to mitochondrial respiration, to detoxification. Cellular heme levels in microbial pathogens can be a composite of endogenous de novo synthesis or exogenous uptake of heme or heme synthesis intermediates. Intracellular pathogenic microbes switch routes for heme supply when heme availability fluctuates in their replicative environment throughout infection. Here, we show that Toxoplasma gondii, an obligate intracellular human pathogen, encodes a functional heme biosynthesis pathway. A chloroplast-derived organelle, termed apicoplast, is involved in heme production. Genetic and chemical manipulation revealed that de novo heme production is essential for T. gondii intracellular growth and pathogenesis. Surprisingly, the herbicide oxadiazon significantly impaired Toxoplasma growth, consistent with phylogenetic analyses that show T. gondii protoporphyrinogen oxidase is more closely related to plants than mammals. This inhibition can be enhanced by 15- to 25-fold with two oxadiazon derivatives, lending therapeutic proof that Toxoplasma heme biosynthesis is a druggable target. As T. gondii has been used to model other apicomplexan parasites, our study underscores the utility of targeting heme biosynthesis in other pathogenic apicomplexans, such as Plasmodium spp., Cystoisospora, Eimeria, Neospora, and Sarcocystis.
    MeSH term(s) Heme/biosynthesis ; Heme/genetics ; Humans ; Phylogeny ; Plant Proteins/metabolism ; Plants/enzymology ; Plants/genetics ; Protoporphyrinogen Oxidase/genetics ; Protoporphyrinogen Oxidase/metabolism ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Toxoplasma/enzymology ; Toxoplasma/genetics ; Toxoplasmosis/enzymology ; Toxoplasmosis/genetics
    Chemical Substances Plant Proteins ; Protozoan Proteins ; Heme (42VZT0U6YR) ; Protoporphyrinogen Oxidase (EC 1.3.3.4)
    Language English
    Publishing date 2020-05-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1008499
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Evidence for involvement of the C-terminal domain in the dimerization of the CopY repressor protein from Enterococcus hirae.

    Pazehoski, Kristina O / Cobine, Paul A / Winzor, Donald J / Dameron, Charles T

    Biochemical and biophysical research communications

    2011  Volume 406, Issue 2, Page(s) 183–187

    Abstract: Metal binding to the C-terminal region of the copper-responsive repressor protein CopY is ... Specific involvement of the 38 C-terminal residues of CopY in dimerization is indicated by zonal and ... the demonstration that an unrelated protein (GB1) can be induced to dimerize by extending its sequence with the C ...

    Abstract Metal binding to the C-terminal region of the copper-responsive repressor protein CopY is responsible for homodimerization and the regulation of the copper homeostasis pathway in Enterococcus hirae. Specific involvement of the 38 C-terminal residues of CopY in dimerization is indicated by zonal and frontal (large zone) size-exclusion chromatography studies. The studies demonstrate that the attachment of these CopY residues to the immunoglobulin-binding domain of streptococcal protein G (GB1) promotes dimerization of the monomeric protein. Although sensitivity of dimerization to removal of metal from the fusion protein is smaller than that found for CopY (as measured by ultracentrifugation studies), the demonstration that an unrelated protein (GB1) can be induced to dimerize by extending its sequence with the C-terminal portion of CopY confirms the involvement of this region in CopY homodimerization.
    MeSH term(s) Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Enterococcus/metabolism ; Protein Multimerization ; Protein Structure, Tertiary ; Repressor Proteins/chemistry ; Repressor Proteins/genetics
    Chemical Substances Bacterial Proteins ; CopY protein, Enterococcus hirae ; Repressor Proteins
    Language English
    Publishing date 2011-02-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2011.01.118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Molecular mechanisms of copper metabolism and the role of the Menkes disease protein.

    Harrison, M D / Dameron, C T

    Journal of biochemical and molecular toxicology

    1999  Volume 13, Issue 2, Page(s) 93–106

    Abstract: Menkes disease is an X-linked, recessive disorder of copper metabolism that occurs in approximately 1 in 200,000 live births. The condition is characterized by skeletal abnormalities, severe mental retardation, neurologic degeneration, and patient ... ...

    Abstract Menkes disease is an X-linked, recessive disorder of copper metabolism that occurs in approximately 1 in 200,000 live births. The condition is characterized by skeletal abnormalities, severe mental retardation, neurologic degeneration, and patient mortality in early childhood. The symptoms of Menkes disease result from a deficiency of serum copper and copper-dependent enzymes. A candidate gene for the disease has been isolated and designated MNK. The MNK gene codes for a P-type cation transporting ATPase, based on homology to known P-type ATPases and in vitro experimentation. cDNA clones of MNK in Menkes patients show diminished or absented hybridization in northern blot experiments. The Menkes protein functions to export excess intracellular copper and activates upon Cu(I) binding to the six metal-binding repeats in the amino-terminal domain. The loss of Menkes protein activity blocks the export of dietary copper from the gastrointestinal tract and causes the copper deficiency associated with Menkes disease. Each of the Menkes protein amino-terminal repeats contains a conserved -X-Met-X-Cys-X-X-Cys- motif (where X is any amino acid). These metal-binding repeats are conserved in other cation exporting ATPases involved in metal metabolism and in proteins involved in cellular defense against heavy metals in both prokaryotes and eukaryotes. An overview of copper metabolism in humans and a discussion of our understanding of the molecular basis of cellular copper homeostasis is presented. This forms the basis for a discussion of Menkes disease and the protein deficit in this disease.
    MeSH term(s) Adenosine Triphosphatases/genetics ; Adenosine Triphosphatases/metabolism ; Amino Acid Sequence ; Animals ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cation Transport Proteins ; Copper/metabolism ; Copper-transporting ATPases ; Disease Models, Animal ; Humans ; Liver/metabolism ; Menkes Kinky Hair Syndrome/genetics ; Menkes Kinky Hair Syndrome/metabolism ; Molecular Sequence Data ; Recombinant Fusion Proteins
    Chemical Substances Carrier Proteins ; Cation Transport Proteins ; Recombinant Fusion Proteins ; Copper (789U1901C5) ; Adenosine Triphosphatases (EC 3.6.1.-) ; Copper-transporting ATPases (EC 3.6.3.54) ; ATP7A protein, human (EC 7.2.2.8)
    Language English
    Publishing date 1999
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1410020-4
    ISSN 1099-0461 ; 1095-6670
    ISSN (online) 1099-0461
    ISSN 1095-6670
    DOI 10.1002/(sici)1099-0461(1999)13:2<93::aid-jbt5>3.0.co;2-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Mechanisms for protection against copper toxicity.

    Dameron, C T / Harrison, M D

    The American journal of clinical nutrition

    1998  Volume 67, Issue 5 Suppl, Page(s) 1091S–1097S

    Abstract: Essential transition metals such as copper, molybdenum, and zinc and nonessential metals like cadmium, mercury, and lead can be toxic at the cellular, tissue, and organ levels when present in excess. To avoid metal-induced toxicity most organisms use a ... ...

    Abstract Essential transition metals such as copper, molybdenum, and zinc and nonessential metals like cadmium, mercury, and lead can be toxic at the cellular, tissue, and organ levels when present in excess. To avoid metal-induced toxicity most organisms use a redundant combination of metal-regulated import inhibition, sequestration, and enhanced export mechanisms. Combinations of these mechanisms are used to form detoxification pathways controlled through metal-binding proteins at transcriptional, translational, or enzymatic levels. In mammalian pathways copper is partially detoxified by sequestration in the metal-binding metallothioneins or export via the copper-translocating ATPases. Copper regulation of these two mechanisms is afforded by specific conformational changes induced in regulatory proteins on metal binding.
    MeSH term(s) Adenosine Triphosphatases/genetics ; Amino Acid Sequence ; Animals ; Carrier Proteins/genetics ; Cation Transport Proteins ; Copper/adverse effects ; Copper/pharmacokinetics ; Copper-transporting ATPases ; Humans ; Inactivation, Metabolic ; Metallothionein/physiology ; Molecular Sequence Data ; Recombinant Fusion Proteins ; Transcriptional Activation
    Chemical Substances Carrier Proteins ; Cation Transport Proteins ; Recombinant Fusion Proteins ; Copper (789U1901C5) ; Metallothionein (9038-94-2) ; Adenosine Triphosphatases (EC 3.6.1.-) ; Copper-transporting ATPases (EC 3.6.3.54) ; ATP7A protein, human (EC 7.2.2.8)
    Language English
    Publishing date 1998
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 280048-2
    ISSN 1938-3207 ; 0002-9165
    ISSN (online) 1938-3207
    ISSN 0002-9165
    DOI 10.1093/ajcn/67.5.1091S
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Toxoplasma gondii requires its plant-like heme biosynthesis pathway for infection.

    Amy Bergmann / Katherine Floyd / Melanie Key / Carly Dameron / Kerrick C Rees / L Brock Thornton / Daniel C Whitehead / Iqbal Hamza / Zhicheng Dou

    PLoS Pathogens, Vol 16, Iss 5, p e

    2020  Volume 1008499

    Abstract: ... production is essential for T. gondii intracellular growth and pathogenesis. Surprisingly, the herbicide ... oxadiazon significantly impaired Toxoplasma growth, consistent with phylogenetic analyses that show T ... biosynthesis is a druggable target. As T. gondii has been used to model other apicomplexan parasites, our study ...

    Abstract Heme, an iron-containing organic ring, is essential for virtually all living organisms by serving as a prosthetic group in proteins that function in diverse cellular activities ranging from diatomic gas transport and sensing, to mitochondrial respiration, to detoxification. Cellular heme levels in microbial pathogens can be a composite of endogenous de novo synthesis or exogenous uptake of heme or heme synthesis intermediates. Intracellular pathogenic microbes switch routes for heme supply when heme availability fluctuates in their replicative environment throughout infection. Here, we show that Toxoplasma gondii, an obligate intracellular human pathogen, encodes a functional heme biosynthesis pathway. A chloroplast-derived organelle, termed apicoplast, is involved in heme production. Genetic and chemical manipulation revealed that de novo heme production is essential for T. gondii intracellular growth and pathogenesis. Surprisingly, the herbicide oxadiazon significantly impaired Toxoplasma growth, consistent with phylogenetic analyses that show T. gondii protoporphyrinogen oxidase is more closely related to plants than mammals. This inhibition can be enhanced by 15- to 25-fold with two oxadiazon derivatives, lending therapeutic proof that Toxoplasma heme biosynthesis is a druggable target. As T. gondii has been used to model other apicomplexan parasites, our study underscores the utility of targeting heme biosynthesis in other pathogenic apicomplexans, such as Plasmodium spp., Cystoisospora, Eimeria, Neospora, and Sarcocystis.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article: Underwriting: a key to healthy capitation agreements.

    Dameron, T H / Fessler, J C

    Healthcare financial management : journal of the Healthcare Financial Management Association

    1996  Volume 50, Issue 9, Page(s) 43–45

    Abstract: In some markets, healthcare providers in integrated delivery systems have been assuming full-risk capitated contracts. Some of these contracts have been profitable, but others have produced inconsistent financial results. These results may reflect ... ...

    Abstract In some markets, healthcare providers in integrated delivery systems have been assuming full-risk capitated contracts. Some of these contracts have been profitable, but others have produced inconsistent financial results. These results may reflect inadequate underwriting practices. For providers and HMO insurers to establish financially successful capitation agreements, they must develop and audit an underwriting process to evaluate the health risk of the population entering the managed care system.
    MeSH term(s) Capitation Fee ; Deductibles and Coinsurance ; Financial Management/methods ; Health Maintenance Organizations/economics ; Health Status Indicators ; Humans ; Risk Assessment ; United States
    Language English
    Publishing date 1996-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605617-9
    ISSN 0735-0732 ; 0018-5639
    ISSN 0735-0732 ; 0018-5639
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Stalking metal-linked dimers.

    Pazehoski, Kristina O / Collins, Tyler C / Boyle, Robert J / Jensen-Seaman, Michael I / Dameron, Charles T

    Journal of inorganic biochemistry

    2008  Volume 102, Issue 3, Page(s) 522–531

    Abstract: Protein dimerization is essential for cellular processes including regulation and biosignalling. While protein-protein interactions can occur through many modes, this review will focus on those interactions mediated through the binding of metal ions to ... ...

    Abstract Protein dimerization is essential for cellular processes including regulation and biosignalling. While protein-protein interactions can occur through many modes, this review will focus on those interactions mediated through the binding of metal ions to the proteins. Selected techniques used to study protein-protein interactions, including size exclusion chromatography, mass spectrometry, affinity chromatography, and frontal zone chromatography, are described as applied to the characterization of the Enterococcus hirae protein CopY. CopY forms a homodimer to control the expression of proteins involved in the homeostasis of cellular copper levels. At the center of the CopY dimerization interaction lies a metal binding motif, -CxCxxxxCxC-, capable of binding Zn(II) or Cu(I). The binding of metal to this cysteine hook motif, one within each monomer, is critical to the dimerization interaction. The CopY dimer is also stabilized by hydrophobic interactions between the two monomers. The cysteine hook metal binding motif has been identified in numerous other uncharacterized proteins across the biological spectrum. The prevalence of the motif gives evidence to the biological relevance of this motif, both as a metal binding domain and as a dimerization motif.
    MeSH term(s) Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Binding Sites ; Chromatography, Affinity ; Copper/chemistry ; Copper/metabolism ; Dimerization ; Metals/chemistry ; Metals/metabolism ; Models, Biological ; Protein Binding ; Proteins/chemistry ; Proteins/metabolism ; Repressor Proteins/chemistry ; Repressor Proteins/metabolism
    Chemical Substances Bacterial Proteins ; CopY protein, Enterococcus hirae ; Metals ; Proteins ; Repressor Proteins ; Copper (789U1901C5)
    Language English
    Publishing date 2008-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 162843-4
    ISSN 1873-3344 ; 0162-0134
    ISSN (online) 1873-3344
    ISSN 0162-0134
    DOI 10.1016/j.jinorgbio.2007.10.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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