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)

The fungus Cryptococcus neoformans is an opportunistic human pathogen that causes a life-threatening meningoencephalitis by expression of virulence factors such as melanin, a black pigment produced by the cell wall-associated enzyme laccase. In previous studies (Heung, L. J., Luberto, C., Plowden, A., Hannun, Y. A., and Del Poeta, M. (2004) J. Biol. Chem. 279, 21144-21153) we proposed that the sphingolipid enzyme inositol-phosphoryl ceramide synthase 1 (Ipc1) regulates melanin production through the generation of diacylglycerol (DAG), which was found to activate in vitro protein kinase C1 (Pkc1). Here, we investigated the molecular mechanisms by which DAG regulates Pkc1 in vivo and the effect of this regulation on laccase activity and melanin synthesis. To this end we deleted the putative DAG binding C1 domain of C. neoformans Pkc1 and found that the C1 deletion abolished the activation of Pkc1 by DAG. Deletion of the C1 domain repressed laccase activity and, consequently, melanin production. Finally, we show that these biological effects observed in the C1 deletion mutant are mediated by alteration of cell wall integrity and displacement of laccase from the cell wall. These studies define novel molecular mechanisms addressing Pkc1-laccase regulation by the sphingolipid pathway of C. neoformans, with important implications for understanding and targeting the Ipc1-Pkc1-laccase cascade as a regulator of virulence of this important human pathogen.
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PMID:The role and mechanism of diacylglycerol-protein kinase C1 signaling in melanogenesis by Cryptococcus neoformans. 1594 43

Laccases constitute a multi-gene family of multi-copper glycoproteins. The barley laccase-like multicopper oxidase (LMCO) gene structure, the DNA sequence polymorphism and putative protein have not yet been described. As part of the study of LMCO in cereals, we have characterized the genomic structure of the putative LMCO gene HvLac1 from the barley variety 'Morex' and mapped HvLac1 on chromosome 4H. The genomic sequence of the HvLac1 gene is 2646 bp long and covers 100% of the coding region. It contains four exons and three introns. In this study, we have described the HvLac1 gene nucleotide polymorphisms (In/Del) in 134 barley varieties. Initial characterization of the barley and rice LMCO and the phylogeny analysis indicate that a monocot LMCO family is composed of five members. There are two high pI isoforms of putative HvLac1 protein derived from two in frame translation start codons with 602aa or 592aa residues. Isoforms differ in their predicted subcellular localization and both isoforms are characterized on C-terminus by the presence of the KDEL-like motif, which contributes to the accumulation of soluble proteins in the endoplasmic reticulum. Our results suggest that this unique feature of HvLac1 could be important for their role in physiological processes.
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PMID:Characterization and mapping of a putative laccase-like multicopper oxidase gene in the barley (Hordeum vulgare L.). 2219 80