Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.2 (laccase)
 4,656 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A gene coding for the multi-copper phenol oxidase laccase has been isolated from the white-rot basidiomycete Trametes versicolor. The gene, which is preceded by a TATA box and a pyrimidine-rich region, is predicted to contain ten introns. The mature translation product, preceded by a 22-residue signal peptide, should consist of 498 residues. Comparisons with Edman degradation data of peptides from T. versicolor laccase strongly suggest that two disulfide bridges are formed by Cys-85/Cys-487 and Cys-117/Cys-205, respectively. The encoded protein contains five Cys, and the sequence surrounding the remaining Cys-452 is consistent with its involvement in the ligation of type-1 copper. Alignment of sequences indicates that T. versicolor laccase displays a Phe at the position corresponding to a residue (Met in ascorbate oxidase and azurin) considered important for the reduction potential of type-1 copper proteins.
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PMID:Characterization of a laccase gene from the white-rot fungus Trametes versicolor and structural features of basidiomycete laccases. 766 13

Melanin formation is a promising target for antifungal development. We screened a collection of 727 compounds that were previously approved for clinical use in humans for inhibition of pigmentation in Cryptococcus gattii, a lethal fungal pathogen that causes damage to both immunocompetent and immunocompromised hosts. The pyrimidine analogues flucytosine (5-fluorocytosine [5-FC]), 5-fluorouracil (5-FU) and carmofur were identified as efficient inhibitors of pigmentation in the C. gattii model. Since melanin synthesis is enzymatically catalyzed by laccase in Cryptococcus, we investigated whether inhibition of pigmentation by the pyrimidine analogues was laccase-mediated. Enzyme activity and expression of LAC genes were not involved in the effects of the pyrimidine analogues, suggesting alternative cellular targets for inhibition of pigmentation. To address this hypothesis, we screened a collection of approximately 8000 mutants of C. gattii that were produced by insertional mutation after incubation with Agrobacterium tumefaciens and identified a gene product required for the anti-pigmentation activity of 5-FC as a beta-DNA polymerase. Reduced expression of this gene affected capsule formation and urease activity, suggesting essential roles in the cryptococcal physiology. These results demonstrate a previously unknown antifungal activity of 5-FC and reveal a promising target for the development of novel antifungals.
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PMID:Pharmacological inhibition of pigmentation in Cryptococcus. 3041 73

Mushrooms are attractive resources for novel enzymes and bioactive compounds. Nevertheless, mushrooms spontaneously form brown pigments during food processing as well as extraction procedures for functional compounds. In this study, the dark browning pigment in the extract derived from the edible mushroom Hericium erinaceus was determined to be caused by the oxidation of endogenous polyphenol compounds by the polyphenol oxidase (PPO) enzyme family. These oxidized pigment compounds were measured quantitatively using a fluorospectrophotometer and, through chelation deactivation and heat inactivation, were confirmed to be enzymatic browning products of reactions by a metalloprotein tyrosinase in the PPO family. Furthermore, a transcript analysis of the identified putative PPO-coding genes in the different growth phases showed that tyrosinase and laccase isoenzymes were highly expressed in the mushroom fruiting body, and these could be potential PPOs involved in the enzymatic browning reaction. A metabolite profiling analysis of two different growth phases also revealed a number of potential enzymatic browning substances that were grouped into amino acids and their derivatives, phenolic compounds, and purine and pyrimidine nucleobases. In addition, these analyses also demonstrated that the mushroom contained a relatively high amount of natural antioxidant compounds that can effectively decrease the browning reaction via PPO-inhibitory mechanisms that inhibit tyrosinase and scavenge free radicals in the fruiting body. Altogether, these results contribute to an understanding of the metabolites and PPO enzymes responsible for the enzymatic browning reaction of H. erinaceus.
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PMID:Antioxidant Compounds for the Inhibition of Enzymatic Browning by Polyphenol Oxidases in the Fruiting Body Extract of the Edible Mushroom Hericium erinaceus. 3270 87