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)

Fe(III), Cu(II), Co(III), and Mn(III) complexes of ovo- and human serum transferrins show resonance enhanced Raman bands near 1600, 1500, 1270, and 1170 cm-1 upon excitation with laser frequencies which fall within the visible absorption bands of those metalloproteins. Comparison of the visible absorption and resonance Raman spectra of the Cu(II)-transferrin complexes with those for the Cu(II) model compound, bis(2,4,6-trichlorophenolato)diimidazolecopper(II) monohydrate, indicates that the resonance Raman bands are due to enhancement of phenolic vibrational modes. For the model (Cu(II) compound, a normal coordinate analysis was used to aid our assignment of the observed resonance bands at 1562, 1463, 1311, and 1122 cm-1 to A1 vibrational modes of the 2,4,6-trichlorophenolato moiety. These assignments are consistent with those made for Cu(II)-transferrins. The latter assignments were based upon calculated A1 frequencies for p-methylphenol (Cummings, D.L., and Wood, J.L. (1974), J. Mol. Struct. 20, 1). The wavelength shifts in the resonance bands for the model compound from those for Cu(II)-transferrins are due to the influence of the chloro substituents on the planar vibrations of phenol. These results clearly identify tyrosine as a ligand in copper binding to transferrins.
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PMID:Resonance Raman spectra of iron(III)-, copper(II)-, cobalt(III)-, and manganese(III)-transferrins and of bis(2,4,6-trichlorophenolato)diimidazolecopper(II) monohydrate, a possible model for copper(II) binding to transferrins. 99 Feb 53

Menkes disease, an X-linked recessive disorder of copper metabolism, has recently been mapped to Xq13.3 by two Menkes patients carrying chromosome rearrangements within this region. The breakpoints have been investigated by nonisotopic in situ suppression hybridization using YACs isolated from this region with the flanking markers DXS56 and PGK1. Three YACs were extending over the breakpoints at Xq13.3 and were shown to be overlapping by partial digest restriction maps, IRS-PCR fingerprinting and by the presence of common cosmid clones. These cosmids were subcloned and one of the single copy probes detected both breakpoints using rare-cutting restriction enzyme digests of the patients. All the results together localize the breakpoints to about 100 kb within the overlapping region of the YACs. Mapping of both breakpoints in a 1 Mb YAC contig implies that these YACs contain at least partially, the gene responsible for Menkes disease.
Hum Mol Genet 1992 Oct
PMID:Characterization of a 1.0 Mb YAC contig spanning two chromosome breakpoints related to Menkes disease. 130 48

The concentration of copper in the livers of Long-Evans rats with cinnamon-like coat color (LEC), in which hepatitis and then hepatomas develop spontaneously, was recently found to be abnormally high. Therefore, we examined the copper concentrations in the livers of LEC F1 backcrosses (LEC F1 x LEC) to determine the linkage of copper accumulation with development of hepatitis. Consistent with a previously reported ratio of rats with hepatitis to rats without hepatitis of about 1:1, hepatitis developed in 14 of 30 F1 backcrosses. The copper concentrations in the livers of all LEC F1 backcrosses with hepatitis were abnormally high and comparable to those of LEC rats. In contrast, the concentrations in all backcrosses without hepatitis were similar to those in normal Long-Evans with agouti coat color or Brown-Norway rats. Copper accumulation was shown to be closely linked with the development of hepatitis in LEC rats and appeared to be a possible cause of hepatitis. The concentrations of copper in the livers of Fischer 344 rats after carbon tetrachloride treatment were in the range for normal liver, indicating that a high copper concentration in the liver is specific to LEC rats and not a specific characteristic of hepatitis. Furthermore, we found that the size and level of ceruloplasmin mRNA in the livers of LEC rats were the same as those in LEA rats and that the size and level of ceruloplasmin polypeptide in their livers and plasma were almost the same as those in LEA rats. Therefore, these results suggest that the copper accumulation is not due to alteration of expression or to gross alteration of the ceruloplasmin gene.
Mol Carcinog 1992
PMID:Genetic linkage between copper accumulation and hepatitis/hepatoma development in LEC rats. 131 58

The effect of copper on the levels of plastocyanin (PC) and cytochrome c553 (cyt-c)-specific transcripts from Anabaena sp. PCC 7937 was investigated. The addition of copper resulted in a marked increase in PC mRNA levels, and a decrease in cyt c mRNA levels. Thus the functional exchange between PC and cyt c seems to be regulated at the mRNA level. The copper-dependent increase in PC and decrease in cyt c mRNA levels was abolished when chloramphenicol was added to the cells. This suggests that de novo synthesis of at least one trans-acting element is required to regulate PC and cyt c mRNA levels. Both PC and cyt c mRNA stability was found to be unaltered under varying Cu2+ regimes. This leads to the conclusion that expression of both genes is regulated at the level of initiation of transcription.
Mol Microbiol 1992 Jun
PMID:Transcriptional regulation of the plastocyanin and cytochrome c553 genes from the cyanobacterium Anabaena species PCC 7937. 132 Jul 27

An expression system that utilized yeast copper metallothionein promoter and ubiquitin fusion technology to express the human estrogen receptor gene in yeast is described. We have studied the biochemical and transcriptional regulatory properties of the human estrogen receptor. The biochemical properties of the yeast expressed receptors are identical to the receptors isolated from human tissue. Estradiol mediated activation of transcription by the receptor was studied by a reporter beta-galactosidase gene where expression was under the control of estrogen response elements. Using this expression system and a hyperpermeable yeast strain we have studied the effects of various antiestrogens on the regulation of estrogen receptor function. We demonstrate that tamoxifen and ICI 164,384 are capable of binding to the receptor but neither antiestrogen was able to block the estradiol mediated increase in transcription. In fact, both antiestrogens exerted weak agonist activity in this system.
J Steroid Biochem Mol Biol 1992 Aug
PMID:Human estrogen receptor regulation in a yeast model system and studies on receptor agonists and antagonists. 132 95

Copper has been suggested to facilitate oxidative tissue injury through a free radical-mediated pathway analogous to the Fenton reaction. By applying the ESR spin-trapping technique, evidence for hydroxyl radical formation in vivo was obtained in rats treated simultaneously with copper and ascorbic acid. A secondary radical spin-trapping technique was used in which the hydroxyl radical formed the methyl radical upon reaction with dimethylsulfoxide. The methyl radical was then detected by ESR spectroscopy as its adduct with the spin trap phenyl-N-t-butylnitrone (PBN). Because copper excreted into the bile from treated animals is expected to be maintained in the Cu(I) state (by ascorbic acid or glutathione), a chelating agent that would redox-stabilize it in the Cu(I) state was used to prevent ex vivo redox chemistry. Bile samples were collected directly into solutions of bathocuproinedisulfonic acid, a Cu(I)-stabilizing agent, and 2,2'-dipyridyl, a Fe(II)-stabilizing agent. If these precautions were not taken, radical adducts were generated ex vivo and could be mistaken for radical adducts generated in vivo and excreted into the bile. Besides the PBN/.CH3 adduct, three other radical adducts were produced in vivo and excreted in bile.
Mol Pharmacol 1992 Oct
PMID:In vivo evidence of hydroxyl radical formation after acute copper and ascorbic acid intake: electron spin resonance spin-trapping investigation. 133 58

The effect of erythropoietin (Ep), a glycoprotein hormone, has been studied on lipid peroxidation induced by Cu2+ and ascorbate in vitro, Mg2+ ATPase activity and spectrin of RBC membrane. Our present investigation reveals that Cu2+ and ascorbic acid increases lipid peroxidation of RBC membrane significantly. It has further been observed that under the same experimental condition spectrin, a major cytoskeleton membrane protein, and Mg(2+)-ATPase activity of RBC membrane decrease significantly. However, exogenous administration of Ep completely restores lipid peroxidation and Mg(2+)-ATPase activity and partially recovers spectrin of RBC membrane.
Mol Cell Biochem 1992 Dec 02
PMID:Effect of Cu(2+)-ascorbic acid on lipid peroxidation, Mg(2+)-ATPase activity and spectrin of RBC membrane and reversal by erythropoietin. 133 13

Experimental data are reported on DNA-cleaving activity of the synthetic netropsin analogs consisting of the two N-propylpyrrole carboxamide units linked covalently through two or three glycine residues to a copper-chelating tripeptide glycyl-glycyl-L-histidine. Incubation of DNA restriction fragment and netropsin analog in the presence of ascorbate, hydrogen peroxide and Cu2+ ions resulted in selective cleavage of the DNA at or near the preferred sites for binding of netropsin analog. A similar cleavage pattern is observed after X-ray irradiation of DNA complexes with netropsin analogs tethered with Cu2+ ions. The cleavage patterns are found to be dependent on the length of the connecting chain between the histidine-containing tripeptide and netropsin analog. The netropsin analog containing three glycine residues in the connecting chain, but not the analog with a shorter linker chain, can generate an intense cleavage of one of the two polynucleotide chains at a position corresponding to the presumed binding site for the dimeric ligand species. More than 50% of the total DNA can be cleaved at this position after X-ray irradiation. From analysis of the nucleotide sequences surrounding the preferred cleavage site on several DNA fragments we found that the consensus is 5'-TTTTNCA*AAA-3', where N is an arbitrary nucleotide. The Cu(2+)-mediated cleavage of DNA occurs at the second adenine (indicated by an asterisk) from the 5'-end of the sequence. The greatest cleavage activity is observed when the molar ratio of Cu2+ to the netropsin analog is equal to 0.5. Evidently, the Cu(2+)-ligated and unligated oligopeptide species interacts with each other to form a heterodimer bound to DNA at the cleavage site. To test the validity of this model we have studied the binding of unligated netropsin analog and netropsin analog complexed with Cu2+ ion to a self-complementary oligonucleotide 5'-GCGTTTTGCAAAACGC-3'. It is found that binding of Cu(2+)-ligated netropsin analog to the DNA oligomer preincubated with unligated form of the oligopeptide is a cooperative process for which interactions between the two bound ligands are responsible. The cooperativity parameter is estimated to be on the order of factor 6. Finally, a model is proposed in which a heterodimer stabilized by interligand beta-sheet binds in the minor DNA groove.
Mol Biol (Mosk)
PMID:[Specific DNA cleavage by an analog of netropsin containing a copper(II) chelating peptide Gly-Gly-His]. 133 38

Three cDNA clones were isolated which code for the ubiquitous chloroplast enzyme, polyphenol oxidase (PPO), from Vicia faba. Analysis of the cloned DNA reveals that PPO is synthesized with an N-terminal extension of 92 amino acid residues, presumed to be a transit peptide. The mature protein is predicted to have a molecular mass of 58 kDa which is in close agreement to the molecular mass estimated for the in vivo protein upon SDS-PAGE. Differences in the DNA sequence of two full-length and one partial cDNA clones indicate that PPO is encoded by a gene family. Analysis of the deduced amino acid sequence shows that the chloroplast PPO shares homology with the 59 kDa PPOs in glandular trichomes of solanaceous species. A high degree of sequence conservation was found with the copper-binding domains of the 59 kDa tomato PPO as well as hemocyanins and tyrosinases from a wide diversity of taxa.
Plant Mol Biol 1992 Oct
PMID:Cloning and characterization of cDNAs coding for Vicia faba polyphenol oxidase. 139 68

Sodium/copper chlorophyllin (CHL) is a water-soluble derivative of chlorophyll that exhibits antimutagenic activity in several short-term genotoxicity assays and inhibits carcinogen-DNA binding in vivo. The effect of CHL pretreatment on the excretion of mutagens in the urine and feces of male Sprague-Dawley rats has been studied using the Salmonella mutagenicity assay. Animals were given 1 percent CHL in the drinking water for 2 days before administering a single dose of 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ) by oral gavage. Rats pretreated with CHL had higher levels of mutagens in the urine and feces compared with animals given IQ alone; 48 hr after IQ administration, the total mutagenic dose excreted was < 4% in controls vs. 18% in rats given CHL. Mutagenicity required the presence of an activation system, was unaffected by treatment with beta-glucuronidase or arylsulfatase, and in both the urine and feces was accounted for by increased elimination of unmetabolized parent compound. The results support the view that CHL may operate in vivo as a "desmutagen" or interceptor molecule, interacting with IQ in the gut and tissues, and reducing carcinogen bioavailability.
Environ Mol Mutagen 1992
PMID:Chlorophyllin-enhanced excretion of urinary and fecal mutagens in rats given 2-amino-3-methylimidazo[4,5-f]quinoline. 139 10


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