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At least 433 records · Page 24Linked to original sources

PubMed2006

Intersite structural rearrangement of the blue copper site induced by substrate binding: spectroscopic studies of a copper-containing nitrite reductase from Alcaligenes xylosoxidans NCIMB 11015.

A copper-containing nitrite reductase from Alcaligenes xylosoxidans NCIMB 11015 has its own unique blue or type 1 copper protein resonance Raman spectrum in the usual Cu-S(Cys) stretching region, nu(Cu-S(Cys)), with a pair of strong peaks at 412 and 420 cm(-1) and a weak peak at 364 cm(-1). The predominantly nu(Cu-S(Cys)) Raman bands at 412, 420, and 364 cm(-1) of the type 1 copper site all shifted to higher frequencies upon binding of nitrite to the type 2 copper site, and the resonance Raman difference spectra progressively intensified with the increments of nitrite ion concentration. Positive support for substrate binding to the type 2 copper is provided by the nu(Cu-S(Cys)) bands in the resonance Raman spectrum of a type 2 copper-depleted enzyme, which is insensitive to the presence of NO2-. The shift to higher frequency of the Raman bands of the type 1 copper center with the addition of nitrite ions suggests a stronger Cu-S(Cys) interaction in the substrate-bound A. xylosoxidans nitrite reductase.

Alcaligenes↗

PubMed2001

Selective extraction of blood plasma exchangeable copper for isotope studies of dietary copper absorption.

Measuring mineral absorption by fecal monitoring is labor-intensive and relies on good volunteer compliance. Blood indicators of absorption could be advantageous and we have developed a method for selective extraction-of recently absorbed (exchangeable) copper based on dialysis of plasma with histidine and subsequent copper extraction using Chelex resin. The potential for measuring copper absorption by transient enrichment of exchangeable copper with the stable isotope 65Cu from an ingested tracer, was also investigated. This method was compared with that of the fecal monitoring technique in a human volunteer, who consumed a 6 mg dose of 65Cu with inhibitors of copper absorption. Holmium was used as a non-absorbable rare-earth marker of unabsorbed tracer excretion, allowing estimation of re-secreted 65Cu (44 microg d(-1)), and hence calculation of true tracer absorption, which was only 10.8%. Monitoring plasma tracer kinetics showed potential for estimation of copper absorption without the need for fecal copper analysis.

Chelating Agents↗

PubMed1979

Copper metabolism in mottled mouse mutants: copper therapy of brindled (Mobr) mice.

Copper therapy was applied to brindled mouse mutants, which suffer from lethal hypocupraemia, by using cuprous and cupric solutions. The method of treatment was a single subcutaneous injection of 50 microgram of copper at 7 days of age. Early effects of the dose were: prevention of the tremors and spasms seen in untreated mutants, raising to normal and near-normal of caeruloplasmin oxidase and lysyl oxidase activities and pigmentation of skin and fur. Growth of mutants was retarded up to 23 days of age, but thereafter they rapidly gained weight to be nearly normal by 60 days of age. At 3 days after injection, copper concentrations in previously deficient mutant organs apart from liver were at least as much as those of treated normals, which had remained unchanged. Copper in mutant livers had increased only slightly in comparison with the normal control. A state of copper deficiency recurred in mutant tissues by 25 days after injection. A solution of Cu+, retained as such by an alkyl polyether, and sebacic acid resulted in greater growth rates after 23 days than did three other copper treatments. Cu+ may have resulted in an improved growth response owing to it being more readily metabolized than C12+. Delayed release of copper from the site of injection may have played an important role.

Animals↗

PubMed1982

The effect of copper supplementation on the concentration of copper in the brain of the brindled mouse.

The brindled mutant mouse is a useful model to study Menkes kinky-hair syndrome. The metabolic dysfunctions in both human and rodent are related to insufficient levels of bioavailable copper. Recently, copper supplementation therapy has been able both to prevent the appearance of various neuropathological changes and to prolong the life of these mutant mice. The optimum conditions for supplementation have been shown to be two intraperitoneal injections on postnatal days 7 and 10. The present study reports on the brain copper concentrations before, during and after the intraperitoneal copper therapy. The results demonstrate that postnatal days 7 and 10 correspond to two important epochs in copper homoeostasis. The supplementation therapy seems to provide sufficient bioavailable copper to respond to the needs of the animal at these crucial time points. The results are discussed in terms of their importance to the human copper disorder.

Age Factors↗

PubMed1996

Magnetic and optical properties of copper-substituted alcohol dehydrogenase: a bisthiolate copper (II) complex.

Replacement of the catalytic Zn(II) in horse liver alcohol dehydrogenase (HLADH) with copper produces a mononuclear Cu(II) chromophore with a ligand set consisting of two cysteine sulphurs, one histidine nitrogen plus one further atom. The fourth ligand to the metal ion and the conformation of the protein may be altered by addition of exogenous ligands and/or the cofactor NADH. Absorbance, CD, low-temperature magnetic CD (MCD) and EPR spectra are presented of copper-substituted HLADH samples in both 'open' and 'closed' conformations and in the presence and absence of the exogenous ligands pyrazole and DMSO. The EPR spectra indicate a strong, predominantly axial field about the copper(II) ion with high copper-thiol (cysteine) covalence. The optical and MCD spectra are interpreted in terms of four d-d transitions to low energy, also reflecting the axial ligand field, and four charge-transfer transitions to copper(II) between 30000 and 16000 cm-1 arising from the two cysteine sulphur atoms which give two pairs of oppositely signed MCD C-terms. These transitions are polarized mainly in the axial plane defined by Cys-46, Cys-174 and His-67. The binary complex formed with pyrazole displays quite different EPR and optical spectra which can be understood in terms of a rotation of the copper hole-orbital away from the axial plane thus decreasing sharply the copper-thiol covalence. The magneto-optical spectra in the presence and absence of DMSO are indistinguishable.

Alcohol Dehydrogenase↗

PubMed1975

Studies on the nature of complexes formed by copper with human alimentary secretions and their influence on copper absorption in the rat.

1. Human gastrointestinal secretions formed soluble copper complexes when labelled in vitro with 64Cu. 2. Copper-binding substances of low molecular weight were demonstrated in the saliva, gastric juice and secretin-stimulated duodenal aspirate of nomal subjects by dialysis and gel-chromatography studies. 3. The nature of the copper complexes formed by secretions obtained from patients with Wilson's disease was similar to that oc complexes formed by secretions of normal subjects. 4. Bile contained a copper-binding fraction of high molecular weight which was more concentrated in gall-bladder than hepatic bile. Between pH 5 and pH 8, this component had a greater binding affinity EDTA at a concentration of 10 mmol/1. 5. Absorption of 64Cu from 64Cu-labelled saliva, gastric juice or L-histidine solution (100 mmol/1) administered intraduodenally into groups of rats was similar to that observed in a control series given [Cu]cupric acetate in sodium chloride solution. In contrast, the absorption of 64Cu from labelled hepatic and gall-bladder bile was significantly reduced. 6. The results suggest that dietary copper forms soluble complexes with the alimentary secretions and that these complexes influence absorption of the metal according to their molecular size. The net uptake of ingested copper from the gut lumen ms, low-molecular-weight ligands in the alimentary secretions and a macromolecular copper-binding complex of bile.

Animals↗

PubMed1997

Crystal structures of the copper and nickel complexes of RNase A: metal-induced interprotein interactions and identification of a novel copper binding motif.

We report the crystal structures of the copper and nickel complexes of RNase A. The overall topology of these two complexes is similar to that of other RNase A structures. However, there are significant differences in the mode of binding of copper and nickel. There are two copper ions per molecule of the protein, but there is only one nickel ion per molecule of the protein. Significant changes occur in the interprotein interactions as a result of differences in the coordinating groups at the common binding site around His-105. Consequently, the copper- and nickel-ion-bound dimers of RNase A act as nucleation sites for generating different crystal lattices for the two complexes. A second copper ion is present at an active site residue His-119 for which all the ligands are from one molecule of the protein. At this second site, His-119 adopts an inactive conformation (B) induced by the copper. We have identified a novel copper binding motif involving the alpha-amino group and the N-terminal residues.

Binding Sites↗

PubMed2000

Copper activation of superoxide dismutase 1 (SOD1) in vivo. Role for protein-protein interactions with the copper chaperone for SOD1.

Insertion of copper into superoxide dismutase 1 (SOD1) in vivo requires the copper chaperone for SOD1 (CCS). CCS encompasses three protein domains: copper binding Domains I and III at the amino and carboxyl termini, and a central Domain II homologous to SOD1. Using a yeast interaction mating system, yeast CCS was seen to physically interact with SOD1, and this interaction required sequences at the predicted dimer interface of CCS Domain II. Interactions with SOD1 also required sequences of Domain III, but not Domain I. Mutations were introduced at the dimer interface of yeast SOD1, and the corresponding mutant failed to interact with CCS. When loaded with copper independent of CCS, this mutant SOD1 exhibited superoxide scavenging activity, but was normally inactive in vivo because CCS failed to recognize the enzyme. Activation of SOD1 by CCS was also examined using an in vivo assay for copper incorporation into SOD1. Yeast CCS was observed to insert copper into a pre-existing pool of apoSOD1 without the need for new SOD1 synthesis or for protein unfolding by the major SSA cytosolic heat shock proteins. Our data are consistent with a model in which prefolded dimers of apoSOD1 serve as substrate for the CCS copper chaperone.

Copper↗

PubMed1978

[Behavior of trace elements copper, zinc and manganese in bovine rumen. 2. Passage rate and course of trace element concentration in rumen as influenced by copper sulfate administration].

In experiments on the distribution of copper, zinc and manganese in fractions of rumen liquor (Wetzel and Menke, 1977 (1)) changes in PEG and in trace element concentration during day-time (between 8 a.m. and 6 p.m.) were measured at 2-hour intervals. Rumen volume was 61 l and passage rate 108 and 128 l/day in the two animals used. Average daily passage was calculated to be 40 mg copper, 98 mg zinc and 371 mg manganese. These values were found to be 11% higher than copper intake and 44 and 68% lower than zinc and manganese intakes, respectively. The differences indicate a remarkable endogenous secretion of copper, and a high absorption of zinc and manganese within the rumen. Concentration (mcg/g dry matter) of copper, zinc and manganese in the bacterial fraction and in total rumen liquor decreased slowly in the first hours after feeding, reaching a minimum after 4 to 6 hours and showed a slight increase thereafter. After addition of copper sulphate the curves mostly became linear. The conclusion is drawn that 1.8 ppm copper in inorganic binding does not lead to changes in trace element concentration to an extent that might be harmful to bacterial fermentation.

Animals↗

PubMed2001

Cytochrome c oxidase deficiency due to mutations in SCO2, encoding a mitochondrial copper-binding protein, is rescued by copper in human myoblasts.

Mutations in SCO2, a cytochrome c oxidase (COX) assembly gene, have been reported in nine infants with early onset fatal cardioencephalomyopathy and a severe COX deficiency in striated muscle. Studies on a yeast homolog have suggested that human Sco2 acts as a copper chaperone, transporting copper to the Cu(A) site on the Cox II subunit, but the mechanism of action remains unclear. To investigate the molecular basis of pathogenesis of Sco2 defects in humans we performed genetic and biochemical studies on tissues, myoblasts and fibroblasts from affected patients, as well as on a recombinant human C-terminal Sco2 segment (22 kDa), bearing the putative CxxxC metal-binding motif. Recombinant Sco2 was shown to bind copper with a 1:1 stoichiometry and to form homomeric complexes in vitro, independent of the metal-binding motif. Immunohistochemistry using antibodies directed against different COX subunits showed a marked tissue-specific decrease in the Cox II/III subunits that form part of the catalytic core, consistent with the differential tissue involvement, but a more uniform distribution of Cox Vab, a nuclear-encoded subunit. Sco2 was severely reduced in patient fibroblasts and myoblasts by immunoblot analysis. Patient fibroblasts showed increased (64)Cu uptake but normal retention values and, consistent with this, the copper concentration was four times higher in Sco2-deficient myoblasts than in controls. COX activity in patient myoblasts was completely rescued by transduction with a retroviral vector expressing the human SCO2 coding sequence, and more interestingly by addition of copper-histidine (300 microM) to the culture medium. Whether the latter is accomplished by the very low residual levels of Sco2 in the patient cells, direct addition of copper to the Cu(A) site, or by another copper-binding protein remains unknown. Whatever the mechanism, this result suggests a possible therapy for the early treatment of this fatal infantile disease.

Amino Acid Motifs↗

PubMed1984

The effects of high dietary zinc and copper deficiency on the activity of copper-requiring metalloenzymes in the growing rat.

The effects of feeding rats high levels of dietary zinc (240 mg Zn/kg diet) on the activities of the copper-requiring metalloenzymes: ceruloplasmin (Cp), cupro -zinc superoxide dismutase (SOD) and cytochrome c oxidase (CCO) were determined. These were compared with those seen during copper deficiency (induced by feeding 0.6 mg Cu/kg diet). The activities of Cp in serum, Cu-Zn SOD in liver and heart, and CCO in heart were significantly reduced in both the high zinc and copper-deficient groups by 2 weeks, when compared to the activities seen in rats fed the control diet (6 mg Cu, 30 mg Zn/kg diet). In animals fed the high zinc diet, the reduction in heart CCO activity followed the decrease seen in heart copper concentration, whereas in blood and liver, the reductions in Cp and SOD activities, respectively, were greater than the reductions seen in copper concentration. Thus, the results of this experiment demonstrate that with high dietary zinc, the reductions seen in the activity of copper-requiring metalloenzymes were similar to those seen during copper deficiency.

Animals↗

PubMed1977

Production of copper coproporphyrin III by Bacillus cereus. II. Regulation of the biosynthesis of coproporphyrin III and its copper complex by oxygen and heavy metal ions.

The effects of oxygen and heavy metal ions on the production of copper coproporphyrin III were studied in Bacillus cereus strain 2. The formation of copper coproporphyrin III was found to be maximum when the cells were cultivated in G-medium at a low level of oxygen supply, but it was suppressed at extremely low oxygen supply levels. When the cells were cultured in metal-free G-medium, neither metal-coproporphyrin III nor coproporphyrin III was formed. In the presence of copper in the medium (400-100 micrometers), the formation of coproporphyrin III copper salt was maximum, but the addition of various heavy metal ions other than copper to the copper-free medium resulted in the formation of neither coproporphyrin III nor its metal chelates. Copper ions appear to be specifically required for coproporphyrin III formation.

Bacillus cereus↗

PubMed2006

Molecular characterization of a conserved archaeal copper resistance (cop) gene cluster and its copper-responsive regulator in Sulfolobus solfataricus P2.

Using a comparative genomics approach, a copper resistance gene cluster has been identified in multiple archaeal genomes. The cop cluster is predicted to encode a metallochaperone (CopM), a P-type copper-exporting ATPase (CopA) and a novel, archaea-specific transcriptional regulator (CopT) which might control the expression of the cop genes. Sequence analysis revealed that CopT has an N-terminal DNA-binding helix-turn-helix domain and a C-terminal TRASH domain; TRASH is a novel domain which has recently been proposed to be uniquely involved in metal-binding in sensors, transporters and trafficking proteins in prokaryotes. The present study describes the molecular characterization of the cop gene cluster in the thermoacidophilic crenarchaeon Sulfolobus solfataricus. The polycistronic copMA transcript was found to accumulate in response to growth-inhibiting copper concentrations, whereas copT transcript abundance appeared to be constitutive. DNA-binding assays revealed that CopT binds to the copMA promoter at multiple sites, both upstream and downstream of the predicted TATA-BRE site. Copper was found to specifically modulate the affinity of DNA binding by CopT. This study describes a copper-responsive operon in archaea, a new family of archaeal DNA-binding proteins, and supports the idea that this domain plays a prominent role in the archaeal copper response. A model is proposed for copper-responsive transcriptional regulation of the copMA gene cluster.

Amino Acid Sequence↗

PubMed1980

Electron paramagnetic resonance of the copper in dopamine beta-monooxygenase. Rapid reduction by ascorbate, the steady-state redox level, chelation with EDTA, and reactivation of the apoenzyme by added copper.

The water-soluble form of dopamine beta-monooxygenase from bovine adrenal medulla was studied. Addition of excess CuSO4 to purified enzyme preparations followed by extensive ultrafiltration against copper-free buffer at pH 7.0, gave preparations with about four copper atoms per enzyme tetramer of Mr 290 000. The enzyme-bound copper was shown by the rapid-freeze technique and electron paramagnetic resonance (EPR) to be reduced by ascorbate at a rate which was faster than the overall catalytic rate; about 10% of the copper was oxidized to Cu(II) during steady-state catalysis in the presence of excess ascorbate. These results support an electron-transfer function of the enzyme-bound copper during catalysis and indicate that the reduction by ascorbate is not the rate-limiting step. The enzyme-bound copper was rapidly chelated by EDTA at pH 7.0., and the apoenzyme thus obtained after dialysis revealed no EPR-detectable copper. Addition of CuSO4 to the apoenzyme gave an EPR spectrum similar to that of the native enzyme, and the apoenzyme was fully reactivated by the optimal concentration of CuSO4 in less than 2 s.

Adrenal Medulla↗

PubMed1983

Gastrointestinal and in vitro release of copper, cadmium, indium, mercury and zinc from conventional and copper-rich amalgams.

Particles of a conventional lathe-cut, a spherical non-gamma 2 and a copper amalgam have been gastrointestinally administered to rats for the purpose of evaluation of the dissolution resistance. The animals were sacrificed after 20 hrs. The contents of copper, cadmium, indium, mercury and zinc in kidney, liver, lung or blood were measured using nuclear tracer techniques. From a copper amalgam an extreme release of copper was demonstrated. This study stimulates the clinical condition of elemental release from swallowed amalgam particles after amalgam insertion or after removal of old amalgam fillings. Specimens of the same types of amalgams were also exposed to artificial saliva for a period of 10 days. The amounts of copper and mercury released were measured with flame and flameless atomic absorption spectrophotometry respectively. The levels of copper and mercury released from the copper amalgam were approximately 50 times those of the two other amalgam types studied.

Animals↗

PubMed1993

A two-component regulatory system required for copper-inducible expression of the copper resistance operon of Pseudomonas syringae.

Specific induction of the copper resistance operon (cop) promoter from Pseudomonas syringae was measured by beta-galactosidase production from a cop promoter-lacZ fusion. Induction of the cop promoter in P. syringae pv. syringae required trans-acting factors from copper resistance plasmid pPT23D, from which cop was originally cloned. Tn5 mutagenesis of pPT23D was used to localize two complementation groups immediately downstream from copABCD. Cloning and sequencing of the DNA in this region revealed two genes, copR and copS, expressed in the same orientation as the cop operon but from a separate constitutive promoter. The amino acid sequence deduced from these genes showed distinct similarities to known two-component regulatory systems, including PhoB-PhoR and OmpR-EnvZ. In addition, CopR showed strong similarity to copper resistance activator protein PcoR from Escherichia coli. Functional chromosomal homologs to copRS activated the cop promoter, in a copper-inducible manner, in copper-resistant or -sensitive strains of P. syringae pv. tomato and other Pseudomonas species. This implies that copper-inducible gene regulation is associated with a common chromosomally encoded function, as well as plasmid-borne copper resistance, in Pseudomonas spp.

Amino Acid Sequence↗

PubMed1977

Menkes' Kinky hair syndrome: studies of copper metabolism and long term copper therapy.

A patient with Menkes' kinky hair syndrome was treated with oral CuSO4. Plasma copper, ceruloplasmin, red cell copper, and 24-hr urine copper excretion remained essentially unchanged. Intravenous copper infusion resulted in a rise of serum ceruloplasmin. During administration of a test meal of 64Cu(NO3)2, the patient was given alternately a volume of 0.9% NaCl or an equal volume of plasma intravenously. Radioactivity found in the blood was unchanged after each infusion period. During 427 days of subcutaneous copper, plasma p-phenylenediamine oxidase activity and plasma copper rose toward normal. Subsequent balance studies showed that the patient was in negative copper balance because of large losses in feces. Scanning electron microscopy demonstrated persistent pili torti.

Brain Diseases, Metabolic↗

PubMed1976

Effects of copper deficiency and copper loading on 67Cu in supernatants of rat organs.

Eleven organs of the rat were studied 1 hr and 24 hr after the intravenous administration of 67CuCl2 and 67Cu-ceruloplasmin. The rats were normal, copper-deficient, or copper-laden. The amounts of stable copper and 67Cu in the whole organ and supernatant fractions, corrected for whole blood copper and 67Cu, were measured. The distribution of supernatant 67Cu was determined in three Sephadex G-100 chromatographic zones: Peak I (150,000 daltons), Peak II (31,000 daltons), and Peak III (11,000 daltons). All organs took up 67Cu from both sources, but there was a tendency for increased uptakes in copper-deficient rats and decreased uptake in copper-laden rats. Only lung, heart, and testis took up more 67Cu from 67Cu-ceruloplasmin than from 67CuCl2. Supernatant 67Cu tended to be in Peak I when the source was 67Cu-ceruloplasmin and in Peak II when the source was 67CuCl2. When 67Cu-ceroloplasmin was added to supernatant fractions in vitro, the 67Cu was in Peak I. However, when 67CuCl2 was added to supernatant fractions, Peak III predominated in kidney, brain, testis, and liver; Peak II predominated in none; and Peak I predominated in spleen, muscle, large and small bowel, stomach, lung, and heart. A high-molecular-weight copper-binding substance seems to be present in organ supernatant fractions.

Animals↗