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

---

Query: EC:3.1.1.5 (neuropathy target esterase)
1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inhibitory effects of MgATP on neuronal nuclear acetyltransferase activities were studied using lyso platelet-activating factor (lyso-PAF, 1-alkyl-sn-glycero-3-phosphocholine) and lysophosphatidylcholine (lyso-PC, 1-acyl-sn-glycero-3-phosphocholine). The nuclear (N1) acetylation of lyso-PC was more profoundly inhibited by MgATP. MgATP did not alter the apparent Km for acetyl-CoA in either acetylation reaction. The inhibitory effects of MgATP were not seen for other nucleotides or MgAMP-PCP. Kinase inhibitors such as staurosporine (1 microM), chelerythrine, and R59022 (diglyceride kinase inhibitor I) did not block the MgATP inhibition of either acetylation. However, the addition of phospholipids to the assays indicated a selective inhibitory effect for PIP (25-50 microM) in the nuclear acetylation of lyso-PAF. When N1 was incubated with [gamma-33P]ATP, phosphatidic acid and PIP were the principal radioactive lipid products. While the extent of MgATP inhibition of lyso-PAF acetylation was similar at different concentrations of lyso-PAF, increasing lyso-PC concentrations greatly decreased the MgATP inhibition seen in lyso-PC acetylations. Nuclear envelopes prepared in the presence of PMSF, and fraction N1 exposed to PMSF, did not show the inhibitory effect of MgATP on lyso-PC acetylation. PMSF (an inhibitor of certain phospholipase and lysophospholipase activities) did not reduce the MgATP inhibition of lyso-PAF acetylation. Arachidonoyl trifluoromethylketone, an inhibitor of cytosolic phospholipases A2 and of lysophospholipase activity associated with cPLA2, also blocked the inhibitory effect of MgATP on lyso-PC acetylation. Using radioactive lyso-PC substrate, fraction N1 produced labeled free fatty acid and phosphatidylcholine. In the presence of acetyl-CoA, the production of radioactive phosphatidylcholine increased almost 6-fold when MgATP was also included in these incubations. In the presence of MgATP and acetyl-CoA, PMSF reduced the levels of radioactive free fatty acid and phosphatidylcholine derived from lyso-PC, while Triacsin C, an inhibitor of acyl CoA synthetase, decreased phosphatidylcholine labeling. These findings suggest that MgATP inhibition of lyso-PC acetylation results from a loss of lyso-PC substrate that is largely mediated by nuclear lysophospholipase, acyl-CoA synthetase and lyso-PC acylation. Thus the neuronal nuclear production of Acyl PAF may be regulated by paths that compete for the lyso-PC substrate. In contrast, the acetylation of lyso-PAF is inhibited by PIP, a product of nuclear PI kinase reactions.
...
PMID:MgATP has different inhibitory effects on the use of 1-acyl-lysophosphatidylcholine and lyso platelet-activating factor acceptors by neuronal nuclear acetyltransferase activities. 963 Jul 21

The Candida albicans PLB1 gene was cloned using a polymerase chain reaction-based approach relying on degenerate oligonucleotide primers designed according to the amino acid sequences of two peptide fragments obtained from a purified candidal enzyme displaying phospholipase activity (Mirbod, F., Banno, Y., Ghannoum, M. A., Ibrahim, A. S., Nakashima, S., Yasuo, K., Cole, G. T., and Nozawa, Y. (1995) Biochim. Biophys. Acta 1257, 181-188). Sequence analysis of a 6.7-kilobase pair EcoRI-ClaI genomic clone revealed a single open reading frame of 1818 base pairs that predicts for a pre-protein of 605 residues. Comparison of the putative candidal phospholipase with those of other proteins in data base revealed significant homology to known fungal phospholipase Bs from Saccharomyces cerevisiae (45%), Penicillium notatum (42%), Torulaspora delbrueckii (48%), and Schizosaccharomyces pombe (38%). Thus, we have cloned the gene encoding a C. albicans phospholipase B homolog. This gene, designated caPLB1, was mapped to chromosome 6. Disruption experiments revealed that the caplb1 null mutant is viable and displays no obvious phenotype. However, the virulence of strains deleted for caPLB1, as assessed in a murine model for hematogenously disseminated candidiasis, was significantly attenuated compared with the isogenic wild-type parental strain. Although deletion of caPLB1 did not produce any detectable effects on candidal adherence to human endothelial or epithelial cells, the ability of the caplb1 null mutant to penetrate host cells was dramatically reduced. Thus, phospholipase B may well contribute to the pathogenicity of C. albicans by abetting the fungus in damaging and traversing host cell membranes, processes which likely increase the rapidity of disseminated infection.
...
PMID:Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. 974 87

Mucolipidosis (ML) II and III are rare autosomal recessively inherited diseases characterized by deficiency of multiple lysosomal enzymes and, as a result, a generalized storage of macromolecules in lysosomes of cells of mesenchymal origin. In ML II and ML III fibroblasts, most, but not all, newly synthesized lysosomal enzymes are secreted into the medium instead of being targeted correctly to lysosomes. Defects in the enzyme UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine-1-phosphotransferase underlie this effect. It is unknown how lysosomal phospholipases are targeted to the lysosomes of fibroblasts. In the present study lysosomal phospholipase activity was determined in delipidated fibroblast homogenates and plasma from ML II and ML III patients and controls using a [3H]choline-labeled phosphatidylcholine. After incubation, residual phosphatidylcholine and its labeled degradation products (lysophosphatidylcholine, glycerophosphorylcholine and choline phosphate) were quantified. We found that ML II and ML III fibroblasts are deficient in lysosomal phospholipase A and C activity. These enzymes were present in elevated amounts in plasma of ML II and ML III patients. These data indicate that phospholipases, like most other lysosomal enzymes in these diseases, are secreted into the blood instead of being targeted specifically to lysosomes. Thus, the mannose-6-phosphate receptor pathway is needed for proper delivery of lysosomal phospholipases to lysosomes. We also found that production of labeled choline phosphate was mainly due to the activity of acid sphingomyelinase instead of phospholipase C under the assay conditions used. Other active lipolytic enzymes were phospholipase A and lysophospholipase. No evidence for phospholipase D activity was found.
...
PMID:Lysosomal phospholipase activity is decreased in mucolipidosis II and III fibroblasts. 998 67

The phytopathogenic oomycete Phytophthora capsici secretes in culture a phospholipase activity. Two enzyme isoforms exhibiting a high phospholipase B activity were isolated by chromatography and electrophoresis. They differ in their apparent molar masses (22 and 32 kDa). Both proteins are glycosylated and share the same N-terminal amino acid sequence up to the 39th residue with a high homology with capsicein, the P. capsici elicitin. Although devoid of phospholipase activity, capsicein was shown by circular dichroism to specifically interact with negatively charged phospholipids, suggesting that the membrane lipids could be a potential target for elicitins.
...
PMID:Characterization of elicitin-like phospholipases isolated from Phytophthora capsici culture filtrate. 1038 29

A recent study demonstrated that phospholipase B (PLB), lysophospholipase (LPL) and lysophopholipase transacylase (LPTA) are secreted by Cryptococcus neoformans var. neoformans and showed that the amount of enzyme production correlated with virulence in mice. The present study characterised the extracellular enzyme activities further by radiometric assays and 31P nuclear magnetic resonance spectroscopy (NMR). All three enzymes were most active between 25 and 40 degrees C. Bovine lung surfactant and its major lipid components, disaturated phosphatidylcholine and phosphatidylglycerol, were the optimal substrates for PLB. Lysophosphatidylcholine was the favoured substrate for LPL and LPTA. PLB and LPL/LPTA were differentially affected by Triton X-100, and palmitoyl carnitine was a potent inhibitor of the three phospholipases. LPL and PLB activities were inhibited by dithiothreitol; N-ethylmaleimide inhibited LPL and LPTA activities. None of the enzymes was inhibited by N-bromosuccinimide or p-bromophenacyl bromide. Cellular disruption experiments indicated that >85% of the phospholipase activities were cell-associated, with LPL and LPTA being more easily released than PLB. At pH 5.5 and 7.0, the heat-inactivated secreted enzyme preparations decreased the viability of human neutrophils. This effect was attenuated by active supernates. The relative activities of the PLB, LPL and LPTA in the environment of neutrophils are likely to determine the fate of these cells in vivo. Both phospholipases and heat-stable substances secreted by C. neoformans at 37 degrees C could contribute to membrane degradation and virulence.
...
PMID:Biochemical and functional characterisation of secreted phospholipase activities from Cryptococcus neoformans in their naturally occurring state. 1045 Sep 96

Microbial pathogens use a number of genetic strategies to invade the host and cause infection. These common themes are found throughout microbial systems. Secretion of enzymes, such as phospholipase, has been proposed as one of these themes that are used by bacteria, parasites, and pathogenic fungi. The role of extracellular phospholipase as a potential virulence factor in pathogenic fungi, including Candida albicans, Cryptococcus neoformans, and Aspergillus, has gained credence recently. In this review, data implicating phospholipase as a virulence factor in C. albicans, Candida glabrata, C. neoformans, and A. fumigatus are presented. A detailed description of the molecular and biochemical approaches used to more definitively delineate the role of phospholipase in the virulence of C. albicans is also covered. These approaches resulted in cloning of three genes encoding candidal phospholipases (caPLP1, caPLB2, and PLD). By using targeted gene disruption, C. albicans null mutants that failed to secrete phospholipase B, encoded by caPLB1, were constructed. When these isogenic strain pairs were tested in two clinically relevant murine models of candidiasis, deletion of caPLB1 was shown to lead to attenuation of candidal virulence. Importantly, immunogold electron microscopy studies showed that C. albicans secretes this enzyme during the infectious process. These data indicate that phospholipase B is essential for candidal virulence. Although the mechanism(s) through which phospholipase modulates fungal virulence is still under investigations, early data suggest that direct host cell damage and lysis are the main mechanisms contributing to fungal virulence. Since the importance of phospholipases in fungal virulence is already known, the next challenge will be to utilize these lytic enzymes as therapeutic and diagnostic targets.
...
PMID:Potential role of phospholipases in virulence and fungal pathogenesis. 1062 94

Phospholipase A(1) (PLA(1)), which catalyzes the hydrolysis of the sn-1 ester bond of diacyl phospholipids, was purified from 100,000 x g supernatant of bonito muscle to homogeneity by ammonium-sulfate precipitation and four consecutive column chromatographies (DEAE anion-exchange, ether-Toyopeal, hydroxylapatite and Toyopeal HW 50S columns). The final preparation showed a single band above the 67-kDa molecular marker on SDS-PAGE, and the molecular mass was determined to be 71.5 kDa by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using bovine serum albumin as a standard for calibration. The N-terminal 8 amino residues were determined to be Ala-Pro-Ala-Glu-Lys-Val-Lys-Try. Regiospecificity of multiple enzyme activities of the PLA(1) was examined using positionally defined synthetic phosphatidylcholine (PC) and lysophosphatidylcholines (LPC). An acyl ester bond at the sn-1 position of PC was exclusively hydrolyzed by phospholipase activity, and 1-acyl LPC was cleaved to fatty acid and glycerophosphocholine by lysophospholipase (LPL) activity. However, the positional isomer, 2-acyl LPC was a poor substrate for LPL activity. PC/transacylation activity was also observed when excess 2-acyl LPC was supplied in the reaction mixture, and fatty acid at the sn-1 position of donor PC was transferred to the sn-1 position of acceptor LPC. These results demonstrate that the multiple enzyme activities of PLA(1), this is lysophospholipase, transacylase as well as phospholipase, have a strict regiospecificity at the sn-1 position of substrates.
...
PMID:Purification and regiospecificity of multiple enzyme activities of phospholipase A(1) from bonito muscle. 1066 67

Infection caused by the fungus Cryptococcus neoformans is potentially fatal. A highly active extracellular phospholipase, demonstrating phospholipase B (PLB), lysophospholipase (LPL) and lysophospholipase/transacylase (LPTA) activities, was purified to homogeneity from C. neoformans using (NH(4))(2)SO(4) fractionation, and hydrophobic-interaction, anion-exchange and gel-filtration chromatography. All three enzyme activities co-purified as a single protein with an apparent molecular mass of 70-90 kDa by SDS/PAGE and 160-180 kDa by gel filtration. The ratio of the three activities remained constant after each purification step. The amino acid composition, as well as the sequences of the N-terminus and of five internal peptide fragments were novel. The protein was an acidic glycoprotein containing N-linked carbohydrate moieties, with pI values of 5.5 and 3.5. The apparent V(max) values for PLB and LPL activities were 12.3 and 870 micromol/min per mg of protein respectively; the corresponding K(m) values were approx. 185.3 and 92.2 microM. The enzyme was active only at acidic pH (pH optimum of 4.0 for PLB and 4.0-5.0 for LPL and LPTA). Enzyme activity did not require added cations, but was inhibited by Fe(3+). LPL and LPTA activities were decreased by 0.1% (v/v) Triton X-100 to 50% of the control value. Palmitoylcarnitine (0.5 mM) inhibited PLB (97% inhibition) and LPL and LPTA activities (35% inhibition) competitively. All phospholipids except phosphatidic acid were degraded by PLB, but dipalmitoyl phosphatidylcholine and dioleoyl phosphatidylcholine were the preferred substrates. This is the first complete description of the purification and properties of a phospholipase, which may be involved in virulence, from a pathogenic fungus.
...
PMID:Purification and characterization of secretory phospholipase B, lysophospholipase and lysophospholipase/transacylase from a virulent strain of the pathogenic fungus Cryptococcus neoformans. 1074 72

The SPO1 gene was cloned and shown to encode an early meiotic transcript specifying a nuclear protein with extensive similarity to fungal and vertebrate phospholipase enzymes. Alteration of a conserved serine residue in the putative phospholipase active site, and presence of the spo1-1 temperature-sensitive mutation, which resides near this site, each result in loss of SPO1 function. The phenotype of a complete deletion indicates that SPO1 is dispensable for vegetative growth, premeiotic DNA synthesis and meiotic recombination. In contrast, it is required for Meiosis I (MI) and Meiosis II (MII) chromosome segregation and spore formation. In a null mutant approximately 75% of cells arrest early at MI spindle pole body (SPB) duplication, approximately 20% arrest at MII, and approximately 5% arrest at spore formation. Progression beyond the first arrest point suggests the existence of functions partially redundant to Spo1 and that Spo1 is required at multiple stages. At present SPO1 is the only known gene required for SPB duplication in meiosis but not in mitosis. Its product may thus play a regulatory (rather than a structural) role in SPB function. The transcriptional program in the spo1 null is similar to the wild type early in meiosis but is significantly delayed at later stages of sporulation. A single gene, CWP1, was recovered as a multicopy suppressor of the spo1 null. CWP1 encodes a cell wall protein with a glycolipid moiety. We propose that, when modified by other lipases, this moiety may substitute for the product(s) of Spo1p lipase activity in meiosis. Based on the similarity of Spo1p to phospholipase B enzymes, its unique role in SPB duplication, and pleiotropic effects on MII, late gene expression and spore formation, we propose that the Spo1 protein participates in a novel meiotic pathway that functions through the SPB to coordinate nuclear division with spore development.
...
PMID:Spo1, a phospholipase B homolog, is required for spindle pole body duplication during meiosis in Saccharomyces cerevisiae. 1085 97

The human pathogenic fungus Cryptococcus neoformans secretes a phospholipase enzyme that demonstrates phospholipase B (PLB), lysophospholipase hydrolase and lysophospholipase transacylase activities. This enzyme has been postulated to be a cryptococcal virulence factor. We cloned a phospholipase-encoding gene (PLB1) from C. neoformans and constructed plb1 mutants using targeted gene disruption. All three enzyme activities were markedly reduced in the mutants compared with the wild-type parent. The plb1 strains did not have any defects in the known cryptococcal virulence phenotypes of growth at 37 degrees C, capsule formation, laccase activity and urease activity. The plb1 strains were reconstituted using the wild-type locus and this resulted in restoration of all extracellular PLB activities. In vivo testing demonstrated that the plb1 strain was significantly less virulent than the control strains in both the mouse inhalational model and the rabbit meningitis model. We also found that the plb1 strain exhibited a growth defect in a macrophage-like cell line. These data demonstrate that secretory phospholipase is a virulence factor for C. neoformans.
...
PMID:Extracellular phospholipase activity is a virulence factor for Cryptococcus neoformans. 1112 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---