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At least 19 recordsLinked to original sources
PubMed1996

Synthesis, Characterization, and Single-Crystal EPR Studies of Three Dinuclear Copper(II) Complexes and One Mixed-Valence Tetranuclear Copper(I)-Copper(II) Cluster with an Asymmetric Imidazole-Containing Tripodal Ligand with Copper(II)-Copper(II) Distances between 3.35 and 3.63 Å

The synthesis and characterization of three dinuclear copper(II) complexes and one mixed-valence tetranuclear cluster with the asymmetric imidazole-containing ligand bis(1,1'-imidazole-2-yl)(4-imidazole-4(5)-yl)-2-azabutane (biib) are described. X-ray crystallographic parameters for the copper complexes are as follows. [Cu(2)(biib)(2)(BF(4))(2)](BF(4))(2)(H(2)O)(4): triclinic, space group P&onemacr;, a = 10.178(1) Å, b = 9.4881(9) Å, c = 11.037(1) Å, alpha = 95.130(10) degrees, beta = 112.20(1) degrees, gamma = 92.142(9) degrees, and Z = 1. [Cu(2)(biib)(2)(NO(3))(2)](NO(3))(2)(H(2)O)(4): monoclinic, space group &Pmacr;2(1)/n, a = 9.207(6) Å, b = 17.0516(6) Å, c = 12.6107(7) Å, beta = 109.82(1) degrees, and Z = 2. [Cu(2)(biib)(2)(CuBr(3))(2)]: monoclinic, space group P2(1)/c, a = 11.583(2) Å, b = 11.864(2) Å, c = 16.070(2) Å, beta = 112.459(12) degrees, and Z = 2. The two Cu(II) ions in all four complexes are coordinated in a square-pyramidal geometry by three imidazole nitrogens and one amine nitrogen donor in the equatorial plane, and each copper ion is weakly coordinated at the axial position by respectively a tetrafluoroborate, a perchlorate, a nitrate, or a tribromocuprate(I) anion. By comparison of the structural data of the four complexes a relationship has been established between the donor strength of the anion and some structural features, like the Cu(II)-Cu(II) distance, of the dinuclear Cu(II)-Cu(II) unit in the four complexes. Single-crystal EPR spectra of [Cu(2)(biib)(2)(BF(4))(2)](BF(4))(2)(H(2)O)(4) were recorded at room temperature at X-band frequencies. The triplet spectra have been fit with nonparallel g and D tensors, whose principle values are as follows: g(xx)() = 2.022(8), g(yy)() = 2.060(7), g(zz)() = 2.211(8), D(x)()(')(x)()(') = -0.0182(9) cm(-)(1), D(y)()(')(y)()(') = -0.081(6) cm(-)(1), D(z)()(')(z)()(') = 0.0264(7) cm(-)(1). The compounds were further characterized and studied by ligand field and by frozen-solution and polycrystalline powder EPR spectroscopy. EPR spectra recorded at 77 K of frozen solutions of the perchlorate complex show that upon dilution in methanol the dinuclear complex reacts to form a mononuclear species.

Journal Article↗
PubMed1993

A new investigation of copper(II)-serine, copper(II)-histidine-serine, copper(II)-asparagine, and copper(II)-histidine-asparagine equilibria under physiological conditions, and implications for simulation models relative to blood plasma.

Some years ago, the application of computer modeling to metal speciation in biofluids was questioned based on the discrepancy between the simulated distribution of copper(II) in blood plasma and related experimental results obtained by Neumann and Sass-Kortsak in reconstituted serum. A recent investigation of the relevant copper(II)-amino acid equilibria reconciled these conflicting data, confirming that the reliability of computer models crucially depends on the data on which they are based. Since then, however, some of the constants of the copper-serine system used in that study have been suspected to be overestimated. This work thus reports the redetermination of copper-serine and copper-histidine-serine formation constants under physiological conditions. In addition, serine being close to asparagine in Neumann and Sass-Kortsak's classification, copper-asparagine and copper-histidine-asparagine equilibria have also been reinvestigated. For asparagine complexes, former constants have been basically confirmed. In contrast, all constants relative to serine have effectively been found lower than the previous ones. The effects of these new data on the stimulated distribution of plasma copper are only minor, but a better agreement is observed relative to Neumann and Sass-Kortsak's models in reconstituted serum.

Asparagine↗
PubMed1994

[Bacteria-reducing properties of copper-containing and non-copper-containing materials. II. Relationship between microbiocide effect of copper-containing materials and copper ion concentration after contamination with moist and dry hands].

The bactericide quality of different materials containing copper (copper, brass, brass-sheet) was tested and particularly the effect of humidity and copper-concentration was examined. In first examinations (I. communication) (19) the materials were contaminated by hands, which were dipped into a suspension of different microorganisms (Micrococcus luteus, Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa). The survival rate of the microorganisms on the surfaces was determined after defined exposure times (0, 5, 30, 60, 120 min). The following ways of contaminating the test materials were chosen: single contamination with wet hands, repeated contamination with wet and dry hands. In this examination the results were tested for statistical significance and in parallel experiments the copper-concentration on the surfaces of the materials was determined. Materials containing copper contaminated with wet hands show a significant bactericide effect after an exposure time of 120 min. The bactericide effect on Micrococcus luteus and Pseudomonas aeruginosa is inhibited after contamination with dry hands. This results can not be explained by a different copper-concentration on the surfaces of the materials, because a statistically significant difference of copper-ion concentrations between contamination with wet and dry hands could not be obtained.

Bacteria↗
PubMed1978

[Use of copper for the support of physiological reproductive processes. 1. Copper level in the serum of castrated male swine after various applications of copper and copper compounds].

Various copper compounds (CuSO4, Cu-glycinate, Cu-lactate, Cu-citrate) were applied subcutaneously, intramuscularly, and intravenously to 17 barrows, doses being up to 50 mg Cu, while doses between 0.5 g and 1.0 g CuSO4 were orally administered. Curves of copper levels in the serum then were checked at different times. In response to intravenous application, copper levels reached maximum values as early as after two minutes and dropped to the normal about 90 minutes from application. Subcutaneous and intramuscular applications had but little effect on serum copper levels, while oral administration actually had none at all.

Animals↗
PubMed1994

Effects of copper concentration on mineral nutrient uptake and copper accumulation in protein of copper-tolerant and nontolerant Lotus purshianus L.

One copper-tolerant and one copper-sensitive inbred line of Lotus purshianus L. derived from a copper mine waste site in Northern California and one inbred line of the same species derived from a pasture next to the mine waste were examined for the effects of excessive copper concentrations on mineral nutrient uptake and accumulation of copper in protein fractions. Plants were grown from seeds for a period of 24 days in a modified Hoagland nutrient solution culture supplemented with 3, 6, and 10 microM copper as copper sulfate. The basal nutrient solution without copper amendment was used as the control treatment. The uptake of Cu found in the roots was 100 times or more than that in the leaves. The root tissue copper concentrations reached a plateau under 6 microM copper treatment. The leaf tissue copper concentrations increased with the increase of copper concentration in the solution culture. No difference in pattern of copper uptake was detected between the copper-tolerant and nontolerant plants. The effects of excessive copper concentrations caused reduction of Ca uptake in the leaf tissue and P uptake in both the root and leaf tissues, and no difference was found between the copper-tolerant and nontolerant plants. Increased tissue copper concentration caused greater reduction of Fe, Mn, and Zn uptake in the nontolerant plants than in the tolerant plants; this difference may be important for the growth of the tolerant plants under conditions of excessive copper concentrations. Protein extracted from the roots and leaves of both the copper tolerant and nontolerant plants was subjected to Sephadex G-75 column separation. Two major peaks of protein fractions were detected. Under low (normal level) copper concentration treatment, the copper-tolerant and nontolerant plants had similar Cu/protein ratios. However, under high copper concentration challenged conditions the copper-tolerant plant had a considerably greater Cu/protein ratio (peak II protein) than the nontolerant plants. The amino acid composition of the copper-rich protein fraction (peak II) extracted from both the tolerant and nontolerant plants demonstrated a high asparate (about 25%) content. The contents of glutamate, cystine, and glycine were about 11, 2.5, and 10%, respectively, and the rest of the amino acids were in a range of 2 to 6%. This pattern of amino acid composition is different from the amino acid composition of the phytochelatin metallothionein-like proteins found in copper-tolerant plants which are very high in cysteine.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1992

Copper tolerance and copper accumulation of herbaceous plants colonizing inactive California copper mines.

Herbaceous plant species colonizing four copper mine waste sites in northern California were investigated for copper tolerance and copper accumulation. Copper tolerance was found in plant species colonizing soils with high concentrations of soil copper. Seven of the eight plant species tested were found at more than one copper mine. The mines are geographically isolated, which makes dispersal of seeds from one mine to another unlikely. Tolerance has probably evolved independently at each site. The nontolerant field control population of Vulpia microstachya displays significantly higher tolerance to copper at all copper concentration levels tested than the nontolerant Vulpia myrous population, and the degree of copper tolerance attained by V. microstachya at the two copper mines was much greater than that found in V. myrous. It suggests that even in these two closely related species, the innate tolerance in their nontolerant populations may reflect their potential for evolution of copper tolerance and their ability to initially colonize copper mine waste sites. The shoot tissue of the copper mine plants of Arenaria douglasii, Bromous mollis, and V. microstachya accumulated less copper than those plants of the same species from the field control sites when the two were grown in identical conditions in nutrient solution containing copper. The root tissue of these mine plants contain more copper than the roots of the nonmine plants. This result suggests that exclusion of copper from the shoots, in part by immobilization in the roots, may be a feature of copper tolerance. No difference in the tissue copper concentration was detected between tolerant and nontolerant plants of Lotus purshianus, Lupinus bicolor, and Trifolium pratense even though the root tissue had more copper than the leaves. It suggests that copper tolerance in these legume species is not due to a mechanism of differential capacity for copper accumulation in the roots. Different mechanisms of copper tolerance may have evolved among the plant species colonizing the northern California copper mine waste sites.

California↗
PubMed1994

Regulation of extracellular copper-binding proteins in copper-resistant and copper-sensitive mutants of Vibrio alginolyticus.

Extracellular proteins of wild-type Vibrio alginolyticus were compared with those of copper-resistant and copper-sensitive mutants. One copper-resistant mutant (Cu40B3) constitutively produced an extracellular protein with the same apparent molecular mass (21 kDa) and chromatographic behavior as copper-binding protein (CuBP), a copper-induced supernatant protein which has been implicated in copper detoxification in wild-type V. alginolyticus. Copper-sensitive V. alginolyticus mutants displayed a range of alterations in supernatant protein profiles. CuBP was not detected in supernatants of one copper-sensitive mutant after cultures had been stressed with 50 microM copper. Increased resistance to copper was not induced by preincubation with subinhibitory levels of copper in the wild type or in the copper-resistant mutant Cu40B3. Copper-resistant mutants maintained the ability to grow on copper-amended agar after 10 or more subcultures on nonselective agar, demonstrating the stability of the phenotype. A derivative of Cu40B3 with wild-type sensitivity to copper which no longer constitutively expressed CuBP was isolated. The simultaneous loss of both constitutive CuBP production and copper resistance in Cu40B3 indicates that constitutive CuBP production is necessary for copper resistance in this mutant. These data support the hypothesis that the extracellular, ca. 20-kDa protein(s) of V. alginolyticus is an important factor in survival and growth of the organism at elevated copper concentrations. The range of phenotypes observed in copper-resistant and copper-sensitive V. alginolyticus indicate that altered sensitivity to copper was mediated by a variety of physiological changes.

Carrier Proteins↗
PubMed1999

Copper status of ewes fed increasing amounts of copper from copper sulfate or copper proteinate.

The Cu status of mature, crossbred ewes fed two sources (CuSO4 vs. Cu proteinate) and three levels (10, 20, or 30 mg/kg) of dietary Cu was determined in a 73-d feeding trial. Ewes (n = 30) were fed a basal diet containing rice meal feed, cottonseed hulls, cottonseed meal, meat and bone meal, cracked corn, and vitamin-mineral supplements at 2.5% of BW to meet NRC requirements for protein, energy, macrominerals, and microminerals, excluding Cu. The basal diet contained 5 mg/kg Cu, 113 mg/kg Fe, .1 mg/kg Mo, and .17% S. Copper sulfate or Cu proteinate was added to the basal diet to supply 10, 20, or 30 mg/kg of dietary copper in a 2x3 factorial arrangement of treatments. Ewes were housed in 3.7- x 9.1-m pens in an open-sided barn. Blood samples were collected on d 28 and 73. Ewes were slaughtered on d 74, and liver and other tissues were collected to determine Cu concentrations. An interaction (P = .08) occurred between source and level for liver Cu. The interaction existed due to an increase in liver Cu concentrations when ewes were fed increasing dietary Cu from CuSO4 but not when fed Cu proteinate diets. There was no source x level interaction (P>.10) for the blood constituents measured. On d 73, plasma ceruloplasmin activity was greater (P<.05) in ewes fed Cu proteinate than in those fed CuSO4 (33.1 vs. 26.8 microM x min(-1) x L(-1)). Increasing the concentration of dietary Cu did not affect (P>.10) plasma ceruloplasmin. Packed cell volume (PCV), red blood cell count (RBC), white blood cell count, whole blood hemoglobin (wHb), plasma hemoglobin, and plasma Cu were similar between sources of Cu. Ewes fed 20 mg/kg Cu had lower (P<.05) PCV, RBC, and wHb than those fed 10 or 30 mg/kg Cu diets. Feeding up to 30 mg/kg Cu from these sources did not cause an observable Cu toxicity during the 73-d period.

Animal Feed↗
PubMedDate not supplied

Ascorbic acid feeding of rats reduces copper absorption, causing impaired copper status and depressed biliary copper excretion.

The feeding of diets enriched with ascorbic acid (10 g/kg) to rats has previously been shown to lower plasma and liver copper concentrations. The present studies corroborate this. We hypothesized that ascorbic acid initially reduces copper absorption, this effect being masked later by the stimulatory effect on copper absorption of the impaired copper status. We also hypothesized that the impaired copper status as induced by ascorbic acid feeding is followed by a diminished biliary excretion of copper in an attempt to preserve copper homeostasis. Our hypotheses are supported by the present studies. Ascorbic acid feeding initially reduced apparent copper absorption, and in the course of the experiment this effect tended to turn over into a stimulatory effect. Copper deficiency, as induced by feeding a diet containing 1 mg Cu/kg instead of 5 mg Cu/kg, systematically increased copper absorption. Biliary excretion of copper in rats given ascorbic acid was unaffected initially but became depressed after prolonged ascorbic acid feeding. A similar time course was seen for fecal endogenous copper excretion that was calculated as the difference between true and apparent copper absorption. Copper deficiency systematically reduced biliary copper excretion and fecal endogenous copper loss.

Animals↗
PubMed1990

Copper status and urinary and salivary copper in young men at three levels of dietary copper.

Eleven young men were confined to a metabolic research unit for 90 d to determine the effect of the amount of dietary copper on copper nutriture. The study was divided into three metabolic periods (MP): 1) with an adequate-copper diet (1.68 mg/d) for 24 d, 2) with a low-copper diet (0.79 mg/d) for 42 d, and 3) with a high-copper diet (7.53 mg/d) for 24 d. Three indices of copper status, urinary copper, and salivary copper were determined at intervals throughout the study. Neither copper status, urinary copper, nor salivary copper differed among MPs. Sweat collections from three subjects suggested that losses of copper through sweat were very low and would not contribute significantly to copper balance. These results suggest that an amount of dietary copper slightly less than 0.8 mg/d is adequate to maintain copper status for greater than or equal to 42 d in normal, healthy men and that neither urinary nor salivary copper is affected by the amount of Cu in the diet.

Adult↗
PubMed1997

N-terminal domains of human copper-transporting adenosine triphosphatases (the Wilson's and Menkes disease proteins) bind copper selectively in vivo and in vitro with stoichiometry of one copper per metal-binding repeat.

N-terminal domains of the Wilson's and Menkes disease proteins (N-WND and N-MNK) were overexpressed in a soluble form in Escherichia coli as fusions with maltose-binding protein, purified, and their metal-binding properties were characterized. Both N-MNK and N-WND bind copper specifically as indicated by the results of metal-chelate chromatography, direct copper-binding measurements, and chemical modification of Cys residues in the presence of different heavy metals. When E. coli cells are grown in the presence of copper, N-MNK and N-WND bind copper in vivo with stoichiometry of 5-6 nmol of copper/nmol of protein. Copper released from the copper-N-MNK and copper-N-WND complexes reacts with the Cu(I)-selective chelator bicinchoninic acid in the absence of reducing agents. This suggests that in proteins, it is bound in reduced Cu(I) form, in agreement with the spectroscopic properties of the copper-bound domains. Copper bound to the domains in vivo or in vitro specifically protects the N-MNK and N-WND against labeling with the cysteine-directed probe; this indicates that Cys residues in the repetitive motifs GMTCXXCXXXIE are involved in coordination of copper. Direct involvement of the N-terminal domains in the binding of copper suggests their important role in copper-dependent functions of human copper-transporting adenosine triphosphatases (Wilson's and Menkes disease proteins).

Adenosine Triphosphatases↗
PubMed2000

Plasma diamine oxidase activity is greater in copper-adequate than copper-marginal or copper-deficient rats.

The object of this study was to determine whether serum diamine oxidase activity could distinguish among adequate, marginal and deficient copper status in rats. Male weanling Sprague-Dawley rats (n = 21) were randomly assigned to one of three dietary regimens, with copper concentrations of 0.52, 1.73 and 6.7 mg/kg diet. On completion of the study, body weights were significantly different among dietary groups, with copper-marginal rats displaying the highest mean weight and copper-deficient rats the lowest. Copper-deficient rats ate significantly less food than the other two groups. Rats fed the three diets had significantly different liver copper concentrations. Liver and heart superoxide dismutase and cytochrome c oxidase activities, and plasma ceruloplasmin and erythrocyte superoxide dismutase activities were significantly lower in the copper-deficient rats than in the other two groups. Plasma diamine oxidase activity was lower in both copper-deficient (0.18 +/- 0.11 U/L) and marginal (0.21 +/- 0.11 U/L) rats compared with copper-adequate rats (3.35 +/- 0.28 U/L). Of the biochemical indices measured, only liver copper concentration (-20%) and plasma diamine oxidase activity (-94%) differed between rats fed copper-marginal and copper-adequate diets. Plasma diamine oxidase activity, therefore, may be a sensitive functional biomarker of suboptimal copper status.

Amine Oxidase (Copper-Containing)↗
PubMed2004

Maintaining copper homeostasis: regulation of copper-trafficking proteins in response to copper deficiency or overload.

Copper is an essential micronutrient that plays a vital role as a catalytic co-factor for a variety of metalloenzymes. The redox chemistry of copper also makes it a potentially toxic metal if not properly used. Therefore, elaborate mechanisms have evolved for controlling its cellular uptake, elimination, and distribution. In the last decade, our understanding of the systems involved in maintaining copper homeostasis has improved considerably with the characterization of copper transporters that mediate cellular copper uptake or efflux and with the identification of copper chaperones, a family of proteins required for delivering copper to specific targets in the cell. Despite the distinct roles of these proteins in copper trafficking, all seem able to respond to changes in copper status. Here, we describe recent advances in our knowledge of how copper-trafficking proteins respond to copper deficiency or overload in mammalian cells in order to maintain copper balance.

Animals↗
PubMed1992

Copper-marginal and copper-deficient diets decrease aortic prostacyclin production and copper-dependent superoxide dismutase activity, and increase aortic lipid peroxidation in rats.

Agonist challenged aortic prostacyclin production was examined in copper-adequate, -marginal and -deficient rats fed AIN-based diets providing 6.7, 1.7 and 0.8 micrograms Cu/g, respectively. Aortic rings were incubated in Krebs-Henseleit salts, 10 mmol/L HEPES buffer, pH 7.4, 95%:5% O2:CO2, 37 degrees C, and equilibrated for 1 h. Equilibrated rings were challenged with buffer (basal), 273.0 nmol/L thrombin and angiotensin II at 84.6 pmol/L and 846.0 pmol/L. Prostacyclin production, determined at 10 minutes by RIA as 6-keto prostaglandin F1 alpha, in basal and 84.6 pmol/L angiotensin II ring incubations was significantly reduced by 28 to 48% in copper-deficient rats. With thrombin or 846.0 pmol/L angiotensin II prostacyclin production was significantly reduced by 18 to 55% in copper-marginal and copper-deficient rats. Copper-dependent superoxide dismutase activity was significantly depressed by 30 and 57% in aortae of copper-marginal and copper-deficient rats. Lipid peroxidation, estimated by the thiobarbituric acid test, was significantly increased by 85% in copper-deficient rats, with a nonsignificant 40% increase in aortae from copper-marginal rats. The results suggest that the decreases in aortic prostacyclin production in aortae from both copper-deficient and copper-marginal rats are associated, in a dose-dependent manner, with copper-dependent superoxide dismutase depression and increases in aortic lipid peroxidation.

Analysis of Variance↗
PubMed1993

Effect of copper level and source (copper lysine vs copper sulfate) on copper status, performance, and immune response in growing steers fed diets with or without supplemental molybdenum and sulfur.

One hundred twenty-six crossbred steers (218 kg initial BW) were used to determine the availability of Cu from copper lysine (CuLys) relative to CuSO4. Steers were assigned to pens (four replicates per treatment) based on BW and initial plasma Cu concentration and fed a corn silage-based diet supplemented with 0 or 5 ppm of Cu from either CuSO4 or CuLys. Half of the steers in each treatment were supplemented with 5 ppm of Mo and .2% S. Molybdenum and S supplementation increased (P < .10) growth rate during the first 21 d. Steers receiving CuSO4 gained more during the first 21 d than did control steers (P < .10) and steers receiving CuLys (P < .01). Growth, feed efficiency, and feed intake were not affected over the entire 98-d trial. Molybdenum and S supplementation decreased (P < .05) plasma Cu concentrations. Plasma Cu concentration was not affected by Cu source. Humoral immune response to ovalbumin was measured on d 7 and 77. Dietary treatment did not affect antibody production at either time. Cell-mediated immunity was measured in vivo on d 7 and 77 using phytohemagglutinin. In vivo cell reactivity was not affected by treatment on d 7 but was reduced (P < .10) by Mo and S supplementation on d 77. In vitro cell reactivity was measured on d 98 using a lymphocyte blastogenesis assay. Unstimulated lymphocytes from steers supplemented with Mo and S had lower (P < .10) uptakes of [3H]thymidine. There were no differences among treatments when lymphocytes were stimulated with pokeweed mitogen or phytohemagglutinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1994

The Saccharomyces cerevisiae copper transport protein (Ctr1p). Biochemical characterization, regulation by copper, and physiologic role in copper uptake.

The CTR1 gene of Saccharomyces cerevisiae encodes a protein required for high affinity copper uptake. The protein is expressed on the plasma membrane, is heavily glycosylated with O-linkages, and exists as an oligomer in vivo. The transcript abundance is strongly regulated by copper availability, being induced by copper deprivation and repressed by copper excess. Regulation occurs at very low, nontoxic levels of available copper and is independent of ACE1, the trans-inducer of yeast metallothionein. Expression of Ctr1p is limiting for copper uptake, since overexpression from a 2 mu high copy number plasmid increases copper uptake. Mutations in CTR1 result in altered cellular responses to extracellular copper, demonstrating a physiologic role for CTR1 in the delivery of copper to the cytosol. A copper-dependent reporter gene construct, CUP1-lacZ, is not expressed in CTR1 mutants to the same level as in wild-type strains, and Cu,Zn superoxide dismutase activity is deficient in these mutants. The growth arrest that occurs in CTR1 mutants grown aerobically in copper-deficient media is attributable to the defect in Cu,Zn superoxide dismutase activity.

Aerobiosis↗
PubMed1989

Variations in the intralobular distribution of copper in the livers of copper-loaded rats in relation to the pathogenesis of copper storage diseases.

There are differences in the hepatic intralobular distribution of copper in copper storage related diseases which may be of pathogenetic significance. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals in an attempt to compare copper distribution in their livers with those in human, canine and ovine copper toxicosis. Copper was found to accumulate almost exclusively in the periportal and mid-zones of the rat liver lobules and was associated with progressive pathological changes which included focal and periportal degeneration and necrosis. This pattern of copper distribution contrasts markedly with the centrilobular retention reported in familial canine copper toxicosis and chronic copper poisoning in sheep which suggests that, in these conditions, a secretory deficiency may be less important than a metabolic zonal defect of intracellular copper metabolism. The pathological changes observed in copper-loaded rats have a different micro-anatomical localization from those in dogs and sheep, but show similarities to the early changes reported in the latter species and indicate the possibility of a similar cellular lesion.

Animals↗
PubMed2003

A redox switch in CopC: an intriguing copper trafficking protein that binds copper(I) and copper(II) at different sites.

The protein CopC from Pseudomonas syringae has been found capable of binding copper(I) and copper(II) at two different sites, occupied either one at a time or simultaneously. The protein, consisting of 102 amino acids, is known to bind copper(II) in a position that is now found consistent with a coordination arrangement including His-1, Glu-27, Asp-89, and His-91. A full solution structure analysis is reported here for Cu(I)-CopC. The copper(I) site is constituted by His-48 and three of the four Met residues (40, 43, 46, 51), which are clustered in a Met-rich region. Both copper binding sites have been characterized through extended x-ray absorption fine structure studies. They represent novel coordination environments for copper in proteins. The two sites are approximately 30 A far apart and have little affinity for the ion in the other oxidation state. Oxidation of Cu(I)-CopC or reduction of Cu(II)-CopC causes migration of copper from one site to the other. This behavior is observed both in NMR and EXAFS studies and indicates that CopC can exchange copper between two sites activated by a redox switch. CopC resides in the periplasm of Gram-negative bacteria where there is a multicopper oxidase, CopA, which may modulate the redox state of copper. CopC and CopA are coded in the same operon, responsible for copper resistance. These peculiar and novel properties of CopC are discussed with respect to their relevance for copper homeostasis.

Amino Acid Sequence↗