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

In this study, cDNA and genomic clones encoding a homologue of the yeast gene anti-oxidant 1 (ATX1) from the white-rot fungus Trametes versicolor, a basidiomycete known to produce several laccase isoenzymes involved in lignin degradation, were identified. This gene, named Trametes ATX homologue (tahA), encodes a protein of 7.9 kDa with 56% identity to the yeast Atx1p sequence. Two different alleles of tahA were obtained that differed mainly in their intervening sequences and in a 425 nt insertion located 183 nt upstream of the transcription start site. tahA is present as one copy per haploid nucleus in T. versicolor, as shown by Southern analysis. Expression of tahA cDNA restored high-affinity iron uptake in a deltaatx1 yeast strain and oxygen sensitivity in a deltasod1 deltasod2 yeast strain, showing that tahA is also a functional homologue of ATX1. The inability of tahA to rescue the deltasod1 phenotype on copper-deficient medium indicated that tahA function is copper-dependent. Sequence analysis of the tahA promoter revealed several motifs that were similar to the conserved motifs found in the copper-regulated metallothionein and Cu, Zn superoxide dismutase genes, CUP1 and SOD1, of Saccharomyces cerevisiae, Neurospora crassa and Candida glabrata. In contrast to its yeast homologue ATX1, tahA is induced under elevated copper concentrations in the medium (>0.25 micro M CuSO(4)) and repressed under copper starvation. The transcription of tahA was analysed in response to copper and iron, and after adding xenobiotica. The results are discussed in relevance to laccase expression.
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PMID:Identification and functional expression of tahA, a filamentous fungal gene involved in copper trafficking to the secretory pathway in Trametes versicolor. 1248 Sep 8

The pathogenic yeast Cryptococcus neoformans (Cn) var. gattii causes meningoencephalitis in healthy individuals, unlike the better known Cn varieties grubii and neoformans, which are common in immunocompromised individuals. The virulence determinants and mechanisms of host predilection are poorly defined for var. gattii. The present study focused on the characterization of a Cu,Zn superoxide dismutase (SOD1) gene knock-out mutant constructed by developing a DNA transformation system. The sod1 mutant was highly sensitive to the redox cycling agent menadione, and showed fragmentation of the large vacuole in the cytoplasm, but no other defects were seen in growth, capsule synthesis, mating, sporulation, stationary phase survival or auxotrophies for sulphur-containing amino acids. The sod1 mutant was markedly attenuated in virulence in a mouse model, and it was significantly susceptible to in vitro killing by human neutrophils (PMNs). The deletion of SOD1 also resulted in defects in the expression of a number of virulence factors, i.e. laccase, urease and phospholipase. Complementation of the sod1 mutant with SOD1 resulted in recovery of virulence factor expression and menadione resistance, and in restoration of virulence. Overall, these results suggest that the antioxidant function of Cu,Zn SOD is critical for the pathogenesis of the fungus, but is dispensable in its saprobic life. This report constitutes the first instance in which superoxide dismutase has been directly implicated in the virulence of a fungal pathogen.
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PMID:Characterization of Cu,Zn superoxide dismutase (SOD1) gene knock-out mutant of Cryptococcus neoformans var. gattii: role in biology and virulence. 1262 21

Lipid rafts have been identified in the membranes of mammalian cells, the yeast Saccharomyces cerevisiae, and the pathogenic fungus Candida albicans. Formed by a lateral association of sphingolipids and sterols, rafts concentrate proteins carrying a glycosylphosphatidylinositol (GPI) anchor. We report the isolation of membranes with the characteristics of rafts from the fungal pathogen Cryptococcus neoformans. These characteristics include insolubility in Triton X-100 (TX100) at 4 degrees C, more-buoyant density within a sucrose gradient than the remaining membranes, and threefold enrichment with sterols. The virulence determinant phospholipase B1 (PLB1), a GPI-anchored protein, was highly concentrated in raft membranes and could be displaced from them by treatment with the sterol-sequestering agent methyl-beta-cyclodextrin (MbetaCD). Phospholipase B enzyme activity was inhibited in the raft environment and increased 15-fold following disruption of rafts with TX100 at 37 degrees C. Treatment of viable cryptococcal cells in suspension with MbetaCD also released PLB1 protein and enzyme activity, consistent with localization of PLB1 in plasma membrane rafts prior to secretion. The antioxidant virulence factor Cu/Zn superoxide dismutase (SOD1) was concentrated six- to ninefold in raft membrane fractions compared with nonraft membranes, whereas the cell wall-associated virulence factor laccase was not detected in membranes. We hypothesize that raft membranes function to cluster certain virulence factors at the cell surface to allow efficient access to enzyme substrate and/or to provide rapid release to the external environment.
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PMID:Lipid rafts in Cryptococcus neoformans concentrate the virulence determinants phospholipase B1 and Cu/Zn superoxide dismutase. 1652 4