Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.10.3.1 (tyrosinase)
9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino-acid sequence of tyrosinase from Neurospora crassa (monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) is reported. This copper-containing oxidase consists of a single polypeptide chain of 407 amino acids. The primary structure was determined by automated and manual sequence analysis on fragments produced by cleavage with cyanogen bromide and on peptides obtained by digestion with trypsin, pepsin, thermolysin, or chymotrypsin. The amino terminus of the protein is acetylated and the single cysteinyl residue 96 is covalently linked via a thioether bridge to histidyl residue 94. The formation and the possible role of this unusual structure in Neurospora tyrosinase is discussed. Dye-sensitized photooxidation of apotyrosinase and active-site-directed inactivation of the native enzyme indicate the possible involvement of histidyl residues 188, 192, 289, and 305 or 306 as ligands to the active-site copper as well as in the catalytic mechanism of this monooxygenase.
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PMID:Amino acid sequence of tyrosinase from Neurospora crassa. 15 Dec 79

Additional parameters for the chloramphenicol acetyltransferase (CAT) activity in spores of S. griseus are substantiated. A linear increase in activity was observed with increasing spore number up to a concentration of 5 x 10(10) spores/ml. Similarly an increase of the chloramphenicol concentration up to 500 mug/ml increased the activity. However, a drastic decrease in activity was noted above this level suggesting inhibition of the enzyme by the substrate. The CAT activity in the spores was highly influenced by the pH of the medium reaching a maximum at pH 6.5. This may suggest that CAT is apparently located to the outer surface of the spores and therefore very sensitive to variations in pH of the medium. The CAT showed a marked specificity for D-threo and D-erythrochloramphenicol, while no activity was observed with L-isomers. The enzyme acetylates D,L-erythrodechlor-chloramphenicol with a yield of 45% as compared to the D-threo parent antibiotic. While the tyrosinase characteristics (melanin formation) of S. griseus was eliminated by acriflavine or ethidium bromide treatment the CAT characteristic was persistent. The melanin negative variants retained all otherproperties of the parent strain including the production of antimicrobial agents; and revertants were not detected. The results suggest that the tyrosinase determinant gene is apparently located on an extrachromosomal element (plasmid). On the other hand, the location of the gene for CAT is not assigned yet. The nature of CAT in growing cells and the spores of S. griseus was investigated. The results show that CAT accumulated during the sporulation phase or the vegetative growth is inducible in nature; therefore the morphogenetic sequence in the strain bears no influence on CAT induction.
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PMID:Biotransformation of antibiotics. II. Investigation of the chloramphenicol acetyltransferase in Streptomyces griseus. 82 95

A model system for testing the efficacy of chemotherapy protocols for metastatic melanoma was established using cell cultures from two brain and three lymph node metastases of melanoma from five different patients. Continuously growing cultures which were positive for tyrosinase activity were analysed regarding their proliferation rate by continuous bromodeoxyuridine (BrdU) labelling and subsequent Hoechst-33258/ethidium bromide flow cytometry. Melanoma cell cultures exhibit a strong sensitivity to BrdU: at 5% oxygen, 50% growth inhibition is attained with 360 +/- 130 microM BrdU (range: 130-520; n = 11) vs 650 +/- 50 microM BrdU (n = 3) for diploid human fibroblasts and 570 +/- 20 microM BrdU (n = 6) for human lymphoid cell lines. Moreover, BrdU sensitivity of melanoma cells is clearly oxygen dependent: 50% growth inhibition at 200 +/- 55 microM (range: 65-400 microM) for 20% oxygen vs 360 +/- 130 microM BrdU for 5% oxygen. The cell cycle kinetic mechanism of BrdU-induced growth inhibition is accumulation of cells in the first cycle G2 phase. On the basis of these results we suggest testing BrdU in chemotherapy protocols for the treatment of metastatic melanoma.
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PMID:Bromodeoxyuridine hypersensitivity of metastatic melanoma cells. 149 Jan 11

Tyrosinase activity, synthesis, mRNA, and its posttranslational processing were compared in hair follicular melanocytes of the C3HHeAvy mouse during eumelanogenesis and phaeomelanogenesis. Tyrosinase activity was increased during eumelanogenesis; this increase was accompanied by an increase in tyrosinase synthesis. Tyrosinase activity was also increased during phaeomelanogenesis, but only to a peak level that was 50% of that during eumelanogenesis. However, tyrosinase synthesis and mRNA levels were the same in follicles during eumelanin and phaeomelanin synthesis. The lower level of tyrosinase activity is, therefore, presumably due to posttranslational regulation. Less tyrosinase was associated with the particulate fraction during phaeomelanogenesis than during eumelanogenesis. Glycosylation of tyrosinase during phaeomelanogenesis was also reduced and may be the mechanism of control. Bromo-adenosine 3,5-cyclic monophosphate sodium salt increased glycosylation in both eumelanin and phaeomelanin, producing follicles; but this did not result in an increased uptake of tyrosinase onto the melanosome membrane. Therefore, although cAMP increased glycosylation of tyrosinase, the uptake of tyrosinase by the melanosome membrane appeared to be regulated by other systems that are limiting during phaeomelanogenesis, resulting in a lower level of tyrosinase activity.
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PMID:Regulation of tyrosinase in hair follicular melanocytes of the mouse during the synthesis of eumelanin and phaeomelanin. 166 73

Tyrosinase synthesis and its regulation in human melanocytes was studied by measuring the incorporation of [35S] methionine into incubated skin biopsies. Tyrosinase was detected in all skin samples with the highest levels in skin type IV and the lowest levels in skin type I. Following psoralen ultraviolet A (PUVA) therapy for several weeks, significant increases in the amounts of tyrosinase were found in skin types III and IV. The presence of alpha-melanocyte-stimulating hormone (alpha-MSH) (100 mumol/l) or the long-acting analogue [Nle4, DPhe7] alpha-MSH (1-10 mumol/l) in the incubation medium failed to alter tyrosinase levels in the skin biopsies taken from patients both before and after receiving PUVA therapy. Bromo-adenosine 3,5-cyclic monophosphate sodium salt (8-bromo-cAMP) (10 mmol/l), on the other hand, increased the amounts of tyrosinase both before and after PUVA, but these effects were only seen in biopsies of type III and IV skin. These results indicate that MSH fails to stimulate tyrosinase synthesis in human melanocytes. Nevertheless, tyrosinase synthesis and its regulation by cyclic AMP-dependent mechanisms could be important control points in the pigmentary response.
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PMID:Tyrosinase synthesis in different skin types and the effects of alpha-melanocyte-stimulating hormone and cyclic AMP. 217 91

Tyrosinase synthesis and its posttranslational processing was compared in hair follicular melanocytes of C3H-HeAvy mice during eumelanogenesis and phaeomelanogenesis. Tyrosinase activity was increased during eumelanogenesis and this was paralleled by an increase in tyrosinase synthesis, as measured by the incorporation of [35S]methionine. Although tyrosinase activity was lower during phaeomelanogenesis there was no change in tyrosinase synthesis. alpha-Melanocyte stimulating hormone (alpha-MSH) increased tyrosinase activity and its synthesis during eumelanogenesis but not during phaeomelanogenesis. Bromo-adenosine 3,5-cyclic monophosphate sodium salt (8-bromo-cAMP) was similarly effective during eumelanogenesis, but unlike alpha-MSH stimulated tyrosinase synthesis during phaeomelanogenesis. This suggests that during phaeomelanogenesis the melanocytes may fail to express MSH receptors. This cannot account for the lower tyrosinase activity, however, for alpha-MSH acts predominantly at the level of tyrosinase synthesis and this was similar during eumelanin and phaeomelanin production. The reduced tyrosinase activity is, therefore, presumably due to some posttranslational change. Accordingly, less tyrosinase was associated with the melanosomal fraction during phaeomelanogenesis than during eumelanogenesis. Glycosylation of tyrosinase, as measured by the incorporation of [3H]glucosamine was also reduced during phaeomelanogenesis. Although 8-bromo-cAMP increased glycosylation of tyrosinase in both eumelanin and phaeomelanin producing melanocytes, it failed to alter the subcellular distribution of the enzyme. It would appear that, although glycosylation of tyrosinase is lower during phaeomelanogenesis, the reduced tyrosinase expression is the result of decreased uptake of tyrosinase by the melanosome.
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PMID:Regulation of tyrosinase synthesis and its processing in the hair follicular melanocytes of the mouse during eumelanogenesis and phaeomelanogenesis. 250 79

The complete amino acid sequence of Streptomyces glaucescens tyrosinase is reported. The molecule consists of 273 amino acids and has a Mr of 30 900 including two copper atoms. The primary structure was determined by a combination of amino acid and DNA sequence analysis. Peptide sequence information was derived from the cyanogen bromide, tryptic, and thermolytic fragments of apotyrosinase by automated Edman degradation and aminopeptidase M and carboxypeptidase C digestions. The nucleotide sequence of the tyrosinase gene cloned into the PvuII site of pBR322 was determined. The enzyme contains no apparent leader peptide despite the fact that it is secreted into the culture medium. As observed for a number of different Streptomyces genes, the tyrosinase gene shows a strong preference (97%) for codons ending in G or C. A comparison of the amino acid sequence of Streptomyces glaucescens tyrosinase with that of Neurospora crassa tyrosinase reveals an overall sequence homology of only 24.2%. However, the sequence homology is much higher in those regions thought to be involved in metal binding of the binuclear active site copper of this monooxygenase.
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PMID:Primary structure of tyrosinase from Streptomyces glaucescens. 300 31

The inhibition of tyrosinases from frog epidermis (Rana esculenta ridibunda), mushroom (Agaricus bisporus) and Harding-Passey mouse melanoma by halides is compared. In all cases, the inhibition is pH dependent, increasing when the pH decreases. The order of inhibition is I- greater than Br- greater than Cl- much greater than F- for frog epidermis tyrosinase, F- greater than I- greater than Cl- greater than Br- for mushroom tyrosinase and F- greater than Cl- much greater than Br- greater than I- for the mouse melanoma enzyme. These results are discussed in terms of the active site accessibility to exogenous ligands. The activation energies of the enzyme-catalysed L-dopa oxidation were also calculated, being the values 6.86, 17.01 and 20.25 kcal/mol for frog epidermis, mushroom and Harding-Passey mouse melanoma, respectively. A relationship between these values and the evolutionary adaptation of these enzymes is proposed.
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PMID:Comparative study of tyrosinases from different sources: relationship between halide inhibition and the enzyme active site. 308 87

Cyanogen bromide (CB) cleavage of Neurospora tyrosinase resulted in four major fragments, CB1 (222 residues), CB2 (82 residues), CB3 (68 residues), and CB4 (35 residues), and one minor overlap peptide CB2-4 (117 residues) due to incomplete cleavage of a methionylthreonyl bond. The sum of the amino acid residues of the four major fragments matches the total number of amino acid residues of the native protein. The amino acid sequences of the cyanogen bromide fragments CB2, CB3, and CB4 were determined by a combination of automated and manual sequence analysis on peptides derived by chemical and enzymatic cleavage of the intact and the maleylated derivatives. The peptides were the products of cleavage by mild acid hydrolysis, trypsin, pepsin, chymotrypsin, thermolysin, and Staphylococcus aureus protease V8. The cyanogen bromide fragment CB1 was found to contain two unusual amino acids whose chemical structure will be presented in the following paper.
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PMID:Primary structure of tyrosinase from Neurospora crassa. I. Purification and amino acid sequence of the cyanogen bromide fragments. 621 Jun 95

To align the four cyanogen bromide peptides of Neurospora tyrosinase whose amino acid sequences were reported in the preceding paper, suitable methionine-containing overlap peptides were isolated. The required peptides were obtained by tryptic, peptic, and thermolytic digestion of the unmodified protein and of the maleylated derivative. From the partial sequence information of these peptides and a cyanogen bromide overlap peptide, the four cyanogen bromide fragments were aligned in the order CB3-CB1-CB4-CB2. These data establish Neurospora tyrosinase as a single-chain protein of 407 amino acids with a molecular weight of 46,000. The single cysteinyl residue 94 was found to be covalently linked via a thioether bridge to histidyl residue 96. The chemical nature of this unusual structure was elucidated by physicochemical analysis of peptides obtained from in vivo 35S, [2,5-3H]histidine, and [5-3H]histidine-labeled Neurospora tyrosinase.
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PMID:Primary structure of tyrosinase from Neurospora crassa. II. Complete amino acid sequence and chemical structure of a tripeptide containing an unusual thioether. 621 Jun 96


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