Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous study, we found that human ceruloplasmin (hCP) promotes iron uptake rather than release in BT325 cells, a human glioma cell line. In this study, we investigated the effect of ferroxidase activity of hCP and different species of ceruloplasmins on CP-mediated iron uptake by the cells. The cells were incubated for 30 min at 37 degrees C with 1 microM 59Fe2+ with or without 150 microg/ml of the untreated and the ferroxidase-defective hCPs (apohCP and heat-inactivated hCP) or different species of ceruloplasmins (human CP, rabbit CP and bovine CP). The untreated hCP induced a significant increase in iron uptake by BT325 cells, while ferroxidase-defective hCPs with (heat-inactivated hCP) or without cooper ions (apohCP) had no such role. The untreated hCP increases significantly internalized iron but not membrane-bound iron, implying that hCP stimulated iron entry into the cell rather than increased extracellular binding of iron to the cell surface. All species of ceruloplasmins could promote iron uptake by the cells and the difference in degree of stimulatory effect among them was insignificant. These results suggested that ferroxidase activity of hCP is essential for the hCP-mediated iron uptake process and also that CP-stimulated iron uptake is not associated with copper ions in the protein, and that the effect of ceruloplasmin on iron uptake by BT325 cells is not species specific.
Brain Res Mol Brain Res 2002 Feb 28
PMID:Effects of ferroxidase activity and species on ceruloplasmin mediated iron uptake by BT325 cells. 1186 3

Carnosine, homocarnosine, and anserine are present in high concentrations in the muscle and brain of many animals and humans. Previous studies showed that these compounds have an antioxidant function. We investigated the protective effects of carnosine and related compounds on the modification of human ceruloplasmin that is induced by H2O2. Carnosine, homocarnosine, and anserine significantly inhibited the fragmentation and inactivation of ceruloplasmin that is induced by H2O2. All three compounds also inhibited the release of copper ion from protein, and the formation of hydroxyl radicals in the ceruloplasmin/H2O2 system. These compounds inhibited the fragmentation of human serum albumin that is induced by the copper-catalyzed oxidation system, as well as by the iron-catalyzed oxidation system. These results suggest that carnosine, homocarnosine, and anserine might protect ceruloplasmin against H2O2-mediated oxidative damage through a combination of copper chelation and free radical scavenging.
Mol Cells 2002 Feb 28
PMID:Protection by carnosine-related dipeptides against hydrogen peroxide-mediated ceruloplasmin modification. 1191 59

Adult and young camel ceruloplasmin (Cp) were isolated and purified using the single-step chromatography on amino ethyl-activated sepharose. There are no differences between the adult and the young camel protein. The molecular mass of the protein, as estimated by SDS-PAGE (denaturant conditions), was approximately 130000 Da. The electrophoretic mobility of camel Cp is slightly higher as compared to human and sheep protein suggesting that the camel Cp is homogeneous, compact and more acid. The copper content was estimated to be 5.8+/-0.3 atoms per molecule. The spectroscopic feature includes an absorption maximum at 610 nm, which could be attributed to type 1 copper. The EPR spectrum was completely devoid of any typical signal of the type 2 copper. The kinetic parameters of the adult camel Cp for the specific activity as p-phenylendiamine oxidase were determined as K(m)=0.42 mM and V(max)=0.93 microM NADH/mn/mg Cp. The optimum pH for the activity was 5.7.
Comp Biochem Physiol B Biochem Mol Biol 2002 Mar
PMID:Purification and partial characterization of camel (Camelus Dromedarius) ceruloplasmin. 1195 33

Efficient iron acquisition is an essential requirement for growth of pathogenic organisms in the iron-poor host environment. In Saccharomyces cerevisiae, high-affinity iron import depends on the multicopper ferroxidase ScFet3. ScFet3 biogenesis in the trans-Golgi compartment requires a copper-transporting P-type ATPase, ScCcc2. Here, we describe the isolation by functional complementation of a Ccc2 homologue from the pathogenic yeast Candida albicans. CaCcc2 is functionally distinct from a previously described C. albicans copper-transporting P-type ATPase, CaCrp1, which appears to be specifically involved in copper detoxification. Regulation of CaCCC2 and the phenotype of the homozygous CaCCC2 deletion indicate that it is required for high-affinity iron import, making it the bona fide CCC2 homologue of C. albicans. Remarkably, in a mouse model of systemic infection, the Caccc2Delta strain displayed robust proliferation and no significant reduction in pathogenicity, suggesting the existence of alternative mechanisms of iron uptake from host tissues. We identify haemin and haemoglobin as potential iron sources that can be used by C. albicans in a CaCcc2-independent manner.
Mol Microbiol 2002 Jun
PMID:Deletion of the copper transporter CaCCC2 reveals two distinct pathways for iron acquisition in Candida albicans. 1206 43

The crystal structures of the Met148Leu and Ser86Asp mutants of rusticyanin are presented at 1.82 and 1.65 A resolution, respectively. Both of these structures have two molecules in the asymmetric unit compared to the one present in the crystal form of the native protein. This provides an opportunity to investigate intramolecular electron transfer pathways in rusticyanin. The redox potential of the Met148Leu mutant ( approximately 800 mV) is elevated compared to that of the native protein ( approximately 670 mV at pH 3.2) while that of the Ser86Asp mutant ( approximately 623 mV at pH 3.2) is decreased. The effect of the Ser86Asp mutation on the hydrogen bonding near the type 1 Cu site is discussed and hence its role in determining acid stability is examined. The type 1 Cu site of Met148Leu mimics the structural and biochemical characteristics of those found in domain II of ceruloplasmin and fungal laccase. Moreover, the native rusticyanin's cupredoxin core and the type 1 Cu site closely resemble those found in ascorbate oxidase and nitrite reductase. Structure based phylogenetic trees have been re-examined in view of the additional structural data on rusticyanin and fungal laccase. We confirm that rusticyanin is in the same class as nitrite reductase domain 2, laccase domain 3 and ceruloplasmin domains 2, 4 and 6.
J Mol Biol 2002 Jul 05
PMID:Crystal structures of the Met148Leu and Ser86Asp mutants of rusticyanin from Thiobacillus ferrooxidans: insights into the structural relationship with the cupredoxins and the multi copper proteins. 1207 84

In various peroxynitrite (PN)-treated proteins, the formations of stable 3-nitrotyrosine (nitration) and labile S-nitrosocysteine (S-nitrosation) were observed by employing rapid Western blot in 6 h. The steps of SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and membrane-blotting were performed at 4 degrees C. It was noted that the intensity of immunoreactive bands specific for anti-nitrotyrosine was stronger than that specific for anti-S-nitrosocysteine. Additionally, the intensity was in the manner of a dose-dependency of PN. Nitration/S-nitrosation were formed in the following treated proteins, including bovine serum albumin (BSA), DNase-1, ceruloplasmin, catalase and hemoglobin (Hb). The incubation of PN-pretreated hemoglobin with 1 mM reduced glutathione (GSH) did not change immunoreactivity significantly. However, the addition of glutathione S-transferase (GST) or glutathione peroxidase (GPX) to the above incubation mixture, resulted in decreased immunoreactivity, suggesting GSH may form a transition complex with PN-pretreated hemoglobin and/or partially reduce/modify the treated hemoglobin, thereby increasing the accessibility for the subsequent modification by GST or GPX. Such decreased immunoreactivity indicates that nitrotyrosine and S-nitrosocysteine of treated hemoglobin was, indeed, further modified via (a) converting -NO2 to -NH2 in tyrosine residues, (b) denitrating -NO2 directly/indirectly in tyrosine residues, and/or (c) changing -S-NO to -SH in cysteine residues, or denitrosation. The findings imply similar enzymatic modifications of proteins may also occur in vivo, and therefore play a pivotal role in the NO-related cellular signaling cascade(s).
Mol Cell Biochem 2002 Apr
PMID:Nitration/S-nitrosation of proteins by peroxynitrite-treatment and subsequent modification by glutathione S-transferase and glutathione peroxidase. 1208 80

Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism with copper accumulation in the liver as well as in the central nervous system. Treatment of WD includes oral chelating agents and diet and it is effective. However, once irreversible damage has occurred, the effect of treatment is diminished and the patient's quality of life is compromised. It is estimated that at least half of the patients with WD remain undiagnosed and die of untreated disease. Early detection of patients presymptomatically has been hampered by the lack of effective methods for mass screening. Recently, a sandwich ELISA method for ceruloplasmin measurement in blood spots was developed. We have used this method to analyze blood specimens collected on filter paper from 3667 children aged 3 months-15 years. The mean value of ceruloplasmin was 30.5+/-9.5 mg/dL. Among these children, we identified one WD case, a 32-month-old boy with markedly reduced ceruloplasmin concentration (2.3 mg/dL). Measurement of CP level in dried blood spot sample is proposed as a reliable method for population screening of WD.
Mol Genet Metab 2002 Jun
PMID:Pilot study of mass screening for Wilson's disease in Korea. 1208 10

Ceruloplasmin (CP) is the major plasma antioxidant and copper transport protein. In a previous study, we showed that the aggregation of human ceruloplasmin was induced by peroxyl radicals. We investigated the effects of antioxidant dipeptides carnosine, homocarnosine and anserine on peroxyl radical-mediated ceruloplasmin modification. Carnosine, homocarnosine and anserine significantly inhibited the aggregation of CP induced by peroxyl radicals. When CP was incubated with peroxyl radicals in the presence of three compounds, ferroxidase activity, as measured by the activity staining method, was protected. All three compounds also inhibited the formation of dityrosine in peroxyl radicals-treated CP. The results suggest that carnosine and related compounds act as peroxyl radical scavenger to protect the protein modification. It is proposed that carnosine and related peptides might be explored as potential therapeutic agents for pathologies that involve CP modification mediated by peroxyl radicals generated in the lipid peroxidation.
Mol Cells 2002 Jun 30
PMID:Carnosine and related dipeptides protect human ceruloplasmin against peroxyl radical-mediated modification. 1213 93

Diiron proteins are found throughout nature and have a diverse range of functions; proteins in this class include methane monooxygenase, ribonucleotide reductase, Delta(9)-acyl carrier protein desaturase, rubrerythrin, hemerythrin, and the ferritins. Although each of these proteins has a very different overall fold, in every case the diiron active site is situated within a four-helix bundle. Additionally, nearly all of these proteins have a conserved Glu-Xxx-Xxx-His motif on two of the four helices with the Glu and His residues ligating the iron atoms. Intriguingly, subtle differences in the active site can result in a wide variety of functions. To probe the structural basis for this diversity, we designed an A(2)B(2) heterotetrameric four-helix bundle with an active site similar to those found in the naturally occurring diiron proteins. A novel computational approach was developed for the design, which considers the energy of not only the desired fold but also alternatively folded structures. Circular dichroism spectroscopy, analytical ultracentrifugation, and thermal unfolding studies indicate that the A and B peptides specifically associate to form an A(2)B(2) heterotetramer. Further, the protein binds Zn(II) and Co(II) in the expected manner and shows ferroxidase activity under single turnover conditions.
J Mol Biol 2002 Aug 30
PMID:Computational de novo design, and characterization of an A(2)B(2) diiron protein. 1220 71

Recently it has been observed that multicopper oxidases are present in a number of microbial genomes, raising the question of their function in prokaryotes. Here we describe the analysis of an mco mutant from the opportunistic pathogen Pseudomonas aeruginosa. Unlike wild-type Pseudomonas aeruginosa, the mco mutant was unable to grow aerobically on minimal media with Fe(II) as sole iron source. In contrast, both the wild-type and mutant strain were able to grow either anaerobically via denitrification with Fe(II) or aerobically with Fe(III). Analysis of iron uptake showed that the mco mutant was impaired in Fe(II) uptake but unaffected in Fe(III) uptake. Purification and analysis of the MCO protein confirmed ferroxidase activity. Taken together, these data show that the mco gene encodes a multicopper oxidase that is involved in the oxidation of Fe(II) to Fe(III) subsequent to its acquisition by the cell. In view of the widespread distribution of the mco gene in bacteria, it is suggested that an iron acquisition mechanism involving multicopper oxidases may be an important and hitherto unrecognized feature of bacterial pathogenicity.
Mol Microbiol 2002 Sep
PMID:The multicopper oxidase of Pseudomonas aeruginosa is a ferroxidase with a central role in iron acquisition. 1235 38


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