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At least 577 records · Page 32Linked to original sources
PubMed2003

Controlled reactions on a copper surface: synthesis and characterization of nanostructured copper compound films.

We report the synthesis of nanostructured copper compound films on a copper surface under mild conditions. A series of low-dimensional structures including Cu(OH)(2) fibers and scrolls, CuO sheets and whiskers, and Cu(2)(OH)(2)CO(3) rods have been successfully grown on the copper surfaces at ambient temperature and pressure. Most of the structures are phase-pure single crystallites. The films were formed by the direct oxidation of copper in aqueous solutions of NaOH with an oxidant (NH(4))(2)S(2)O(8). The evolution of the ultrafine structures as a function of the reaction conditions has been revealed, from fibers of Cu(OH)(2) to scrolls of Cu(OH)(2) to sheets or whiskers of CuO. By replacing NaOH with NaHCO(3) in the synthesis, square/rectangular rod arrays of Cu(2)(OH)(2)CO(3) were obtained. The controlled reactions allow the large-scale, template-free, cost-effective synthesis of copper compound films with ordered, uniform, stable, ultrafine structures.

Journal Article↗
PubMed2004

In situ reduction of copper(II) forming an unusually air stable linear complex of copper(I) with a fluorescent tag.

A new fluorescent ligand (phi(f) = 0.8 in dioxane), 2-(4'-aminophthalimidomethyl)pyridine (L), has been synthesized. A one-pot synthesis of its copper(I) complex upon reduction of copper(II) is achieved at room temperature. This complex, which has been characterized by X-ray crystallography, shows a linear N-Cu-N geometry with Cu-N bond lengths of 1.89 A. X-ray structure reveals weak Cu...O interactions between copper and one of the imide oxygen atoms of the ligand framework. Additional weak Cu...O interactions between copper and oxygen atoms of the ClO(4)(-) counteranion are detected that lead to a zigzag polymeric chain with alternate ClO(4)(-) and copper ions. A 2-D intermolecular hydrogen bonding network is also observed. This complex is found to be highly inert toward oxidation both in the solid state and in solution.

Journal Article↗
PubMed2004

New pyridine carboxamide ligands and their complexation to copper(II). X-Ray crystal structures of mono-, di, tri- and tetranuclear copper complexes.

Seven new pyridine dicarboxamide ligands H2L(1-7) have been synthesised from condensation reactions involving pyridine-2,6-dicarboxylic acid (H2dipic), pyridine-2,6-dicarbonyl dichloride or 2,6-diaminopyridine with heterocyclic amine or carboxylic acid precursors. Crystallographic analyses of N,N'-bis(2-pyridyl)pyridine-2,6-dicarboxamide monohydrate (H2L8 x H2O), N,N'-bis[2-(2-pyridyl)methyl]pyridine-2,6-dicarboxamide and N,N'-bis[2-(2-pyridyl)ethyl]pyridine-2,6-dicarboxamide monohydrate revealed extensive intramolecular hydrogen bonding interactions. 2,6-Bis(pyrazine-2-carboxamido)pyridine (H2L6) and 2,6-bis(pyridine-2-carboxamido)pyridine (H2L7) reacted with copper(II) acetate monohydrate to give tricopper(II) complexes [Cu3(L)2(mu2-OAc)2]. X-Ray crystallography confirmed deprotonation of the amidic nitrogen atoms and that the (L6,7)2- ligands and acetate anions hold three copper(II) ions in approximately linear fashion. H2L8. Reacted with copper(II) tetrakis(pyridine) perchlorate to give [Cu(L8)(OH2)]2 x 2H2O, in which (L8)2- was tridentate through the nitrogen atoms of the central pyridine ring and the deprotonated carboxamide groups at one copper centre, with one of the terminal pyridyl rings coordinating to the other copper atom in the dimer. The corresponding reaction using H2L7 gave [Cu3(L7)2(py)2][ClO4]2, which transformed during an attempted recrystallisation from ethanol under aerobic conditions to a tetracopper(II) complex [Cu4(L7)2(L7-O)2].

Journal Article↗
PubMed1980

Coordination environment and fluoride binding of type 2 copper in the blue copper protein ascorbate oxidase.

The coordination environment of the type 2 (nonblue) copper in native ascorbate oxidase (L-ascorbate:oxygen oxidoreductase, EC 1.10.3.3) and of a derivative of the enzyme having the type 1 (blue) copper reversibly bleached has been examined by electron paramagnetic resonance (EPR) spectroscopy. In the g[unk] region of the spectrum of bleached ascorbate oxidase, a seven-line superhyperfine pattern is seen that is attributed to the presence of three nitrogen-donor ligands to a type 2 copper having tetragonal geometry. The superhyperfine splitting patterns in the g parallel region of the EPR spectra of native and bleached ascorbate oxidase show that as many as two fluorides may bind to type 2 copper. Because fluoride inhibits the enzyme competitively with respect to ascorbic acid, it is proposed that the type 2 copper is part of the ascorbate binding site.

Journal Article↗
PubMed2003

Measurement of cytoplasmic copper, silver, and gold with a lux biosensor shows copper and silver, but not gold, efflux by the CopA ATPase of Escherichia coli.

Copper, silver, gold and other heavy metals are potentially toxic to cells. Copper is also essential and cellular levels must be carefully controlled. In contrast, there is no known biological role for silver or gold and they have not been recognized as metals that are under homeostatic control. Using a luminescent biosensor based of the Vibrio fischeri lux gene cluster under the control of the Escherichia coli copA promoter/CueR metal-responsive regulator, we could show that in E. coli, cytoplasmic copper and silver, but not gold, are regulated by the CopA ATPase, the major copper efflux pump.

Adenosine Triphosphatases↗
PubMed2001

The role of copper in topa quinone biogenesis and catalysis, as probed by azide inhibition of a copper amine oxidase from yeast.

All known copper amine oxidases (CAOs) contain 2,4,5-trihydroxyphenylalanine quinone (TPQ) as a redox cofactor. TPQ is derived posttranslationally from a specific tyrosine residue within the protein itself, and is utilized by the enzyme to oxidize amines to aldehydes. Several oxidative mechanisms for both turnover and the biogenesis of the cofactor have been proposed in recent years, which differ mainly in the nature of the interaction of oxygen with the enzyme. In this study, azide is used to probe the role of copper in catalysis and biogenesis, especially with respect to potential interactions between the metal and oxygen. During turnover, it is found that azide is a noncompetitive inhibitor with respect to O(2), most consistent mechanistically with oxygen binding off the metal prior to reaction. During biogenesis, it is found that azide likely prohibits ligation of the precursor tyrosine to the copper, thus preventing the formation of this key intermediate. This result is consistent with previous proposals, where the copper-tyrosine unit is the species that undergoes reaction with O(2). In addition, it is found that oxygen consumption is kinetically uncoupled from TPQ formation; this leads to an expanded kinetic model for biogenesis, with important implications for previous results.

Amine Oxidase (Copper-Containing)↗
PubMed2006

Relationship of stopped flow to steady state parameters in the dimeric copper amine oxidase from Hansenula polymorpha and the role of zinc in inhibiting activity at alternate copper-containing subunits.

The expression of a copper amine oxidase (CAO) from Hansenula polymorpha in Saccharomyces cerevisiae under differing culture conditions leads to the incorporation of varied levels of CAO-bound zinc. The presence of substantial amount of zinc results in two distinctive enzyme species, designated as the fast and slow enzymes. Both forms are rapidly reduced by substrate methylamine with a rate constant of 199 s(-1) but behave remarkably differently in their oxidation rates; the fast enzyme is oxidized by dioxygen at a rate of 22.1 s(-1), whereas the slow enzyme reacts at a rate of 1.8 x 10(-4) s(-1). The apparent kcat of the enzyme preparation is linearly proportional to the fraction of the fast enzyme, with an extrapolated value of 6.17 s(-1) when the enzyme is 100% in its "fast" form. A comparison of rate constants for cofactor reduction and reoxidation steps, measured in stopped flow experiments, to the extrapolated kcat implicates additional steps in the steady state reaction. Measurement of the proportion of oxidized (ETPQ(ox)) and reduced cofactor (ETPQ(red)) under steady state conditions indicates approximately 50% of each cofactor form at 0.8 or 2 mM methylamine. Kinetic isotope effect measurements using deuterated amine substrate lead to the following steady state values: (D)(k(red)) = 8.5 (0.5), (D)(kcat) = 1.7 (0.1), and (D)(kcat/K(m)) = 4.3 (0.2). The collective data allow the calculation of partially rate-determining constants during the reductive half-reaction (ca. 200 s(-1) for binding of substrate to ETPQ(ox) and 27.9 s(-1) for release of aldehyde product or a protein isomerization from ETPQ(red)); an additional step with a rate constant of 13.2 s(-1) is assigned to the oxidative half-reaction, most likely for the release of product hydrogen peroxide. These results, together with the sole detection of oxidized and reduced cofactor during rapid scanning stopped flow experiments, indicate that four steps contribute to kcat, with the first electron transfer from cofactor to O2 contributing ca. 29%. An investigation of the relationship between the copper content and the extent of the fast enzyme shows that only the copper-containing homodimer is capable of rapid reoxidation and that zinc-copper heterodimers are incapable of rapid turnover at either subunit. This implies communication between the metal sites of the two subunits per dimer that impacts O2 binding and/or electron transfer from reduced cofactor to bound O2.

Amine Oxidase (Copper-Containing)↗
PubMed2000

Investigation of spectroscopic intermediates during copper-binding and TPQ formation in wild-type and active-site mutants of a copper-containing amine oxidase from yeast.

Copper amine oxidases possess the unusual ability to generate autocatalytically their organic cofactor, which is subsequently utilized in turnover. This cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), is formed within the active site of these enzymes by the oxidation of a single tyrosine residue. In vitro, copper(II) and oxygen are both necessary and sufficient for the conversion of tyrosine to TPQ. In this study, the biogenesis of TPQ has been characterized in an amine oxidase from Hansenula polymorpha expressed as the apo-enzyme in Escherichia coli. With the WT enzyme, optical absorbances which are copper or oxygen dependent are observed and characterized. Active-site mutants are used to investigate further the nature of these spectral species. Evidence is presented which suggests that tyrosine is activated for reaction with oxygen by liganding to Cu(II). In the following paper in this issue [Schwartz, B., Dove, J. E., and Klinman, J. P. (2000) Biochemistry 39, 3699-3707], the initial reaction of precursor protein with oxygen is characterized kinetically. Taken together, the available data suggest a mechanism for the oxidation of tyrosine to TPQ where the role of the copper is to activate substrate.

Amine Oxidase (Copper-Containing)↗
PubMed2004

C-terminal domain of the membrane copper transporter Ctr1 from Saccharomyces cerevisiae binds four Cu(I) ions as a cuprous-thiolate polynuclear cluster: sub-femtomolar Cu(I) affinity of three proteins involved in copper trafficking.

The cytosolic C-terminal domain of the membrane copper transporter Ctr1 from the yeast Saccharomyces cerevisiae, Ctr1c, was expressed in E. coli as an oxygen-sensitive soluble protein with no significant secondary structure. Visible-UV spectroscopy demonstrated that Ctr1c bound four Cu(I) ions, structurally identified as a Cu(I)(4)(micro-S-Cys)(6) cluster by Xray absorption spectroscopy. This was the only metalated form detected by electrospray ionization mass spectrometry. An average dissociation constant K(D) = (K(1)K(2)K(3)K(4))(1/4) = 10(-)(19) for binding of Cu(I) to Ctr1c was estimated via competition with the ligand bathocuproine disulfonate bcs (beta(2) = 10(19.8)). Equivalent experiments for the yeast chaperone Atx1 and an N-terminal domain of the yeast Golgi pump Ccc2, which both bind a single Cu(I) ion, provided similar K(D) values. The estimates of K(D) were supported by independent estimates of the equilibrium constants K(ex) for exchange of Cu(I) between pairs of these three proteins. It is apparent that, in vitro, the three proteins buffer "free" Cu(I) concentrations in a narrow range around 10(-)(19) M. The results provide quantitative support for the proposals that, in yeast, (a) "free" copper concentrations are very low in the cytosol and (b) the Cu(I) trafficking gradient is shallow along the putative Ctrlc --> Atx1 --> Ccc2n metabolic pathway. In addition, both Ctr1c and its copper-responsive transcription factor Mac1 contain similar clusters which may be important in signaling copper status in yeast.

Amino Acid Sequence↗
PubMed2005

Metal-responsive transcription factor (MTF-1) handles both extremes, copper load and copper starvation, by activating different genes.

From insects to mammals, metallothionein genes are induced in response to heavy metal load by the transcription factor MTF-1, which binds to short DNA sequence motifs, termed metal response elements (MREs). Here we describe a novel and seemingly paradoxical role for MTF-1 in Drosophila in that it also mediates transcriptional activation of Ctr1B, a copper importer, upon copper depletion. Activation depends on the same type of MRE motifs in the upstream region of the Ctr1B gene as are normally required for metal induction. Thus, a single transcription factor, MTF-1, plays a direct role in both copper detoxification and acquisition by inducing the expression of metallothioneins and of a copper importer, respectively.

Animals↗
PubMed1994

Copper levels & reactive oxygen species in uterine flushings in copper intrauterine contraceptive device users.

Copper levels were estimated in the uterine flushings in 15 copper 'T' 200 device acceptors. There was a statistically significant difference in the preinsertion and one week post insertion values (P < 0.001). This also corresponded to a high level of generation of reactive oxygen species. The levels of reactive oxygen species were similar to preinsertion values at 4 and 12 wk. The copper values declined over the 3 months but were still higher at 12 wk as compared to preinsertion levels and this difference was statistically significant. Hence addition of copper to the intrauterine device besides enhancing the contraceptive efficacy, perhaps also plays an important role in microbicidal activity and helps in overcoming the infection introduced at the time of insertion.

Adult↗
PubMed1999

Crystallographic structures of bovine copper-zinc superoxide dismutase reveal asymmetry in two subunits: functionally important three and five coordinate copper sites captured in the same crystal.

A key feature of the generally accepted catalytic mechanism of CuZn superoxide dismutase (CuZnSOD) is the breakage of the imidazolate bridge between copper and zinc and the loss of a coordinated water molecule from copper on reduction from Cu(II) to Cu(I). Crystal structures exist for the enzyme from a number of sources in the oxidised, five coordinate copper form. For the reduced form two structures from different sources have been determined only recently but provide contradictory results. We present crystal structures of bovine CuZnSOD (BSOD) in two different space groups. The structure of the P212121 form (pBSOD), at 1.65 A resolution clearly shows one subunit with Cu in the five coordinate, oxidised form, and the other with Cu in the three coordinate form expected for the reduced state. This mixed state of pBSOD is confirmed by XANES data of these crystals. The pBSOD structure has thus captured each subunit in one of the two oxidation state conformations and thus provides direct crystallographic evidence for the superoxide dismutase mechanism involving the breakage of the imidazole bridge between Cu and Zn. A shift in the position of copper in subunit A poises the catalytic centre to undergo the first stage of catalysis via dissociation of Cu from His61 with a concomittant movement of the coordinated water molecule towards His61, which rotates by approximately 20 degrees, enabling it to form a hydrogen bond to the water molecule. The Cu-Zn separation in the reduced site is increased by approximately 0.5 A. In contrast the 2.3 A resolution structure in space group C2221 (cBSOD) shows both of the Cu atoms to be in the five coordinate, oxidised form but in this space group the whole of subunit A is significantly more disordered than subunit B. An examination of published structures of "oxidised" SODs, shows a trend towards longer Cu-Zn and Cu-His61 separations in subunit A, which together with the structures reported here indicate a potential functional asymmetry between the subunits of CuZnSODs. We also suggest that the increased separation between Cu and Zn is a precursor to breakage of His61.

Animals↗
PubMed1993

Cu/Zn superoxide dismutase activity does not parallel copper levels in copper supplemented HL-60 cells.

The objective of this research was to develop a method for measuring Cu/Zn-superoxide dismutase (Cu/Zn-SOD) (E.C. 1.15.1.1) in HL-60 cells and subsequently examine the relationship between cellular copper levels and the activity of this copper-requiring enzyme. In cells such as the neutrophil or HL-60 promyelocyte cell line, the activity of Cu/Zn-SOD cannot be measured because of an increase in the oxidation rate of the substrate by some unknown compound in the cells. Others have utilized heat treatment to inactivate the responsible compounds, however, we found that heat treatment of HL-60 cells resulted in a loss of over half of the activity of the enzyme. The method described here utilizes sodium azide to inhibit the substance(s) that are responsible for the enhanced rate of pyrogallol's oxidation. Gel filtration data confirmed that the compound responsible for the enhanced rate of pyrogallol oxidation was sensitive to azide and did not affect Cu/Zn-SOD activity. When HL-60 cells were incubated with various levels of copper, Cu/Zn-SOD activity did not reflect the cellular copper levels.

Azides↗
PubMedDate not supplied

Models for enzyme-copper-nucleic acid interaction. 1H NMR line broadening study of the interaction of some copper complexes with cytidine.

Sodium (salicylideneglycylglycinato) copper(II), bis(2,9-dimethyl-1, 10-phenanthroline)copper (II), and (1,5-bis (benzimidazol-2-yl)-3-thiapentane) copper(II) were interacted with cytidine in D2O. For all the complexes, the broadening of the 1H signals of cytidine is found to be in the order H(5) greater than H(6) greater than H(1'); this suggests the binding of N (3) and O2 sites of cytidine to copper. The possibility that the ribose moiety is also involved in coordination cannot be ruled out. The complete broadening of the H(5) signals for the last complex above is because of the coordinative unsaturation of the complex. It has been concluded that steric factors and coordinative unsaturation in the complexes affect the extent of interaction with cytidine.

Binding Sites↗
PubMed1991

Copper supplementation effects on indicators of copper status and serum cholesterol in adult males.

Two 6-wk double-blind studies evaluated the effects of supplements of 2 or 3 mg Cu/d on serum copper, ceruloplasmin, red-blood-cell super oxide dismutase (RBC-SOD), total serum cholesterol, and serum lipoprotein-cholesterol fractions in adult males. Study I had 6 supplemented and 8 placebo subjects, whereas study II had 7 and 6, respectively. Copper supplementation did not appear to affect serum copper levels, RBC-SOD, hematocrit, and ceruloplasmin levels when assayed by radial immunoassay diffusion. Supplementation with 2 mg Cu/d produced an increase in LDL cholesterol and the percentage of cholesterol as LDL at wk 4 compared to the placebo group, and a concomitant decline in VLDL-cholesterol levels and the percentage of cholesterol as VLDL. At wk 6, the percentage of cholesterol as LDL increased and that of cholesterol as VLDL decreased compared to baseline values in the supplemented group. Supplements of 3 mg Cu/d increased hemoglobin levels, ceruloplasmin activity, and serum total-cholesterol levels at wk 6 compared to placebos. Differences in cholesterol may be partly explained by variability in the placebo groups in both studies. Copper supplementation effects on cholesterol deserves further investigation.

Adult↗
PubMed2002

Mechanism of copper resistance in a copper mine isolate Pseudomonas putida strain S4.

The mechanism of copper resistance in a multiple-metal-resistant natural isolate Pseudomonas putida strain S4 is based on inducible efflux. Active extrusion of copper ions occurs from the cytoplasm during the exponential phase of growth. Involvement of ATPase in the efflux of copper ions has been demonstrated by employing specific inhibitors. The effluxed copper is not thrown out of the cell, but remains in a bound form (to a protein) in the periplasm. Thus, a balance between the intracellular level, to fulfill the metabolic requirements, and the periplasmic sequestration, to evade toxicity, is maintained by this isolate.

Copper↗
PubMed2006

Pi-pi interaction between aromatic ring and copper-coordinated His81 imidazole regulates the blue copper active-site structure.

Noncovalent weak interactions play important roles in biological systems. In particular, such interactions in the second coordination shell of metal ions in proteins may modulate the structure and reactivity of the metal ion site in functionally significant ways. Recently, pi-pi interactions between metal ion coordinated histidine imidazoles and aromatic amino acids have been recognized as potentially important contributors to the properties of metal ion sites. In this paper we demonstrate that in pseudoazurin (a blue copper protein) the pi-pi interaction between a coordinated histidine imidazole ring and the side chains of aromatic amino acids in the second coordination sphere, significantly influences the properties of the blue copper site. Electronic absorption and electron paramagnetic resonance spectra indicate that the blue copper electronic structure is perturbed, as is the redox potential, by the introduction of a second coordination shell pi-pi interaction. We suggest that the pi-pi interaction with the metal ion coordinated histidine imidazole ring modulates the electron delocalization in the active site, and that such interactions may be functionally important in refining the reactivity of blue copper sites.

Amino Acid Substitution↗
PubMed2005

Disruption of the copper efflux pump (CopA) of Serratia marcescens ATCC 274 pleiotropically affects copper sensitivity and production of the tripyrrole secondary metabolite, prodigiosin.

The prodigiosin biosynthetic gene cluster (pig cluster) of Serratia marcescens ATCC 274 (Sma 274) is flanked by cueR/copA homologues. Inactivation of the copA homologue resulted in an increased sensitivity to copper, confirming that CopA is involved in copper homeostasis in Sma 274. The effect of copper on the biosynthesis of prodigiosin in Sma 274 and the copA mutant strain was investigated. Increased levels of copper were found to reduce prodigiosin production in the wild type Sma 274, but increase production in the copA mutant strain. The physiological implications for CopA mediated prodigiosin production are discussed. We also demonstrate that the gene products of pigB-pigE of Sma 274 are sufficient for the biosynthesis of 2-methyl-3-n-amyl-pyrrole and condensation with 4-methoxy-2,2'-bipyrrole-5-carboxyaldehyde to form prodigiosin, as we have shown for Serratia sp. ATCC 39006.

Bacterial Proteins↗