Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.5 (neuropathy target esterase)
 1,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Escherichia coli thioesterase I (TAP) is a multifunctional enzyme possessing activities of thioesterase, esterase, arylesterase, protease, and lysophospholipase. In particular, TAP has stereoselectivity for amino acid derivative substrates, hence it is useful for the kinetic resolution of racemic mixtures of industrial chemicals. In the present work, the crystal structure of native TAP was determined at 1.9A, revealing a minimal SGNH-hydrolase fold. The structure of TAP in complex with a diethyl phosphono moiety (DEP) identified its catalytic triad, Ser10-Asp154-His157, and oxyanion hole, Ser10-Gly44-Asn73. The oxyanion hole of TAP consists of three residues each separated from the other by more than 3.5A, implying that all of them are highly polarized when substrate bound. The catalytic (His)C(epsilon1)-H...O=C hydrogen bond usually plays a role in the catalytic mechanisms of most serine hydrolases, however, there were none present in SGNH-hydrolases. We propose that the existence of the highly polarized tri-residue-constituted oxyanion hole compensates for the lack of a (His)C(epsilon1)-H...O=C hydrogen bond. This suggests that members of the SGNH-hydrolase family may employ a unique catalytic mechanism. In addition, most SGNH-hydrolases have low sequence identities and presently there is no clear criterion to define consensus sequence blocks. Through comparison of TAP and the three SGNH-hydrolase structures currently known, we have identified a unique hydrogen bond network which stabilizes the catalytic center: a newly discovered structural feature of SGNH-hydrolases. We have defined these consensus sequence blocks providing a basis for the sub-classification of SGNH-hydrolases.
J Mol Biol 2003 Jul 11
PMID:Crystal structure of Escherichia coli thioesterase I/protease I/lysophospholipase L1: consensus sequence blocks constitute the catalytic center of SGNH-hydrolases through a conserved hydrogen bond network. 1284 70

Cytoskeletal components play an important role in maintaining cellular architecture and internal organization, with clear involvement of defining cell shape, in cell division and other cellular processes, such as neurite extension and maintenance. Alterations of cytoskeleton in human neuroblastoma SK-N-SH cells after exposure to different concentrations of tri-ocresyl phosphate (TOCP) for 12 hr were investigated. TOCP decreased the cell viability in a dose-dependent manner; the viability of SK-N-SH was reduced to approximately 50% of baseline after a 12-hour exposure to TOCP at high concentration (5 mM). Biochemical characterization by western blotting revealed that 1 and 5 mM concentrations of TOCP significantly inhibited the expression of neurofilament high molecular weight protein (NF-H), and that 5 mM TOCP inhibited expression of microtubule-associated protein 2c and tau protein, but not beta-actin. Indirect immunofluorescence analysis revealed that higher concentrations of TOCP decreased the length of neuritis and changed the structure of microfilaments, which are associated with NF-H. In addition, activities of neuropathy target esterase and acetylcholinesterase were significantly reduced after exposure to 5 mM TOCP for 12 hr. Together, these results suggested that the loss of cytoskeletal components is the early event during the process of TOCP toxicity towards human neuroblastoma SK-N-SH cells.
Mol Cell Biochem 2006 Oct
PMID:Effect of tri-o-cresyl phosphate on cytoskeleton in human neuroblastoma SK-N-SH cell. 1690 9

Modifications in dietary fatty acid intake might lead to a modification in membrane phospholipid fatty acid composition. The purpose of this study was to investigate relationship between different type of oil consumption and leukocyte membrane phospholipid composition. This study was carried out in subjects utilizing butter (n = 15), margarine (n = 15), fluid oil (n = 15) and mixed types of oils (n = 15) in total 60 subjects. Leukocytes were separated from total blood by dextran sedimentation method. Membrane lipids and proteins were isolated following the cell disruption. Fatty acids of membrane phospholipids were isolated by hydrolysation with phospholipase B under ultrasonic dismembranator. Free fatty acids were identified with gas chromatography at chloroform phase. The results obtained were compared with data obtained by chromatograms of the standards. Results more prominent values of arachidic, dihomo-gamma-linolenic and palmitoleic acids were found in butter-or mixed oil-user groups; eicosadienoic, eicosamonoenoic, dihomo-gamma-linolenic and behenic acids in fluid oil heptanoic, valeric, eicosadienoic and linolenic acids in margarine groups. The fatty acid composition of mixed oil; was similar to butter, while other two oils were so different. From this study, it was concluded that the type of oil consumption might have an influence on phospholipid components of plasma membranes.
J Biochem Mol Biol 2006 Sep 30
PMID:Determination of saturated and unsaturated Fatty acids amount in leukocyte membranes from subjects fed with solid and fluid oils. 1700 71

Chelicerates are a diverse group of arthropods, with around 65,000 described species occupying a wide range of habitats. Many phylogenies describing the relationships between the various chelicerate orders have been proposed. While some relationships are widely accepted, others remain contentious. To increase the taxonomic sampling of species available for phylogenetic study based on mitochondrial genomes we produced the nearly complete sequence of the mitochondrial genome of the scorpion Mesobuthus gibbosus. Mitochondrial gene order in M. gibbosus largely mirrors that in Limulus polyphemus but tRNA secondary structures are truncated. A recent analysis argued that independent reversal of mitochondrial genome strand-bias in several groups of arthropods, including spiders and scorpions, could compromise phylogenetic reconstruction and proposed an evolutionary model that excludes mutational events caused by strand-bias (Neutral Transitions Excluded, NTE). An arthropod dataset of six mitochondrial genes, when analyzed under NTE, yields strong support for scorpions as sister taxon to the rest of Chelicerata. We investigated the robustness of this result by exploring the effect of adding additional chelicerate genes and taxa and comparing the phylogenies obtained under different models. We find evidence that (1) placement of scorpions arising at the base of the Chelicerata is an artifact of model mis-specification and scorpions are strongly supported as basal arachnids and (2) an expanded chelicerate dataset finds support for several proposed interordinal relationships (ticks plus mites [Acari] and spiders plus whip spiders plus whip scorpions [Araneae+Pedipalpi]). Mitochondrial sequence data are subject to systematic bias that is positively misleading for evolutionary inference and thus extreme methodological care must be taken when using them to infer phylogenies.
Mol Phylogenet Evol 2007 May
PMID:The effect of model choice on phylogenetic inference using mitochondrial sequence data: lessons from the scorpions. 1727 51

NTE-related esterase (NRE), conserved in mouse, rat and human, was a member of patatin-like phospholipases (PLPLA) with high homology to neuropathy target esterase (NTE). Little has been known about the characteristics of NRE and NRE functional esterase activity has yet not been defined. The C-terminal gene sequence of mouse NRE (mNREC) encoding 923-1,326 amino acid containing the patatin domain was first cloned and then expressed tagged with enhanced green fluorescence protein (EGFP) in mammalian cells. The results showed that mNREC had NTE esterase activity in mammalian cells. Overexpression of mNREC did not affect the esterase activity sensitive to paraoxon or resistant to both paraoxon and mipafox. mNREC was distributed in the cytoplasm in contrast to the distribution of human NTE esterase domain. The expression analysis of NRE gene in adult mouse tissues by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) showed that there were higher levels of NRE mRNA in the brain and testis than in the liver and kidney, which was about 50% and 35% of that in the brain. These results firstly showed the tissue distribution of NRE gene in adult mouse and defined that NRE had functional esterase activity.
Mol Cell Biochem 2007 Dec
PMID:Molecular cloning and expression of the C-terminal domain of mouse NTE-related esterase. 1767 53

A mammalian family of lipid hydrolases, designated "patatin-like phospholipase domain containing (PNPLA)" recently has attracted attention. NTE-related esterase (NRE) as a member of PNPLA is an insulin-regulated lysophospholipase with homology to neuropathy target esterase (NTE). Mouse NRE (mNRE) has a predicted amino-terminal transmembrane region (TM), a putative regulatory (R) domain, and a hydrophobic catalytic (C) domain. In the current study, we described the expression of green fluorescent protein (GFP)-tagged constructs of mNRE and mutant proteins lacking the specific protein domains. Esterase assays indicated that neither the TM nor R-domain was essential for mNRE esterase activity, but the TM significantly contributed to its activity. Subcellular distribution showed that mNRE was anchored in ER via its TM domain and that its C-domain was associated with ER. Furthermore, experiments involving proteinase treatment revealed that most of mNRE molecule was exposed on the cytoplasmic face of ER membranes. Collectively, our results for the first time revealed the protein domains, catalytic activity, and subcellular location of mNRE and a simplified model for mNRE was proposed.
Mol Cell Biochem 2010 Jun
PMID:Protein domains, catalytic activity, and subcellular distribution of mouse NTE-related esterase. 2328 90

To identify a predictor to forecast superovulation response on the basis of associations between superovulation performance and gene polymorphism, the PCR-RFLP method was applied to detect an A>G transition determining an MspI polymorphism at position 192 in the exon I of the bovine inhibin alpha (INHA) gene and evaluate its associations with superovulatory response in 118 Chinese Holstein cows treated for superovulation. Association analysis showed that cows with the GG genotype resulted in a significant increase in the number of ova (TNO) than AG and AA genotypes in the first (P=0.023), second (P=0.004) and third (P=0.002) superovulation treatments and produced more transferable embryos (NTE) than that of AG and AA genotypes in the third (P=0.045) superovulation treatment. Moreover, individuals with GG genotype produced more transferable embryos than AA (P<0.05) genotype in the second superovulation treatment and all cows without superovulation response were mutations with genotypes of AA and AG. These results indicate that INHA gene can be used as a predictor for superovulation in Chinese Holstein cows, and imply that cows with AA genotype should be excluded for superovulation practices.
Mol Biol Rep 2011 Jan
PMID:An MspI polymorphism in the inhibin alpha gene and its associations with superovulation traits in Chinese Holstein cows. 2023 72

Neuropathy target esterase (NTE) is a novel phospholipase B and plays a role in phospholipid homeostasis. Although over-expression of NTE inhibits cell division, the role of NTE in cell proliferation is still unknown. In the current study, we firstly used synchronous HeLa cells to study the expression profile of NTE during the cell cycle. NTE protein and activity are regulated during the cell cycle with highest level at G1 and lowest at G2/M phase. However, NTE mRNA levels are constant during the cell cycle. The role of NTE in cell proliferation was investigated by short hairpin RNA (shRNA) to suppress the expression of NTE. Knockdown of NTE significant down-regulated of NTE expression and reduced the glycerophosphocholine level. However, suppression of NTE did not affect phosphatidylcholine content or cell cycle progression. In addition, NTE was demonstrated to be degraded by the ubiquitin-proteasome pathway. These results suggested for the first time that NTE is a cell cycle-dependent protein, but is not essential for cell proliferation, and the ubiquitin-mediated proteolysis may be involved in the regulation of NTE during the cell cycle.
Mol Biol Rep 2011 Jan
PMID:The role of cell cycle-dependent neuropathy target esterase in cell proliferation. 2030 2

NTE-related esterase (NRE) is a novel endoplasmic reticulum-anchored lysophospholipase with high homology to neuropathy target esterase (NTE). However, little is known about the regulation of NRE protein. In the current study, we investigated the degradation pathways of mouse NRE (mNRE) in mammalian cells. Based on experiments with inhibitors and inducer of protein degradation pathways, we provide here the first evidence that mNRE is degraded by macroautophagy as well as by the proteasome. Moreover, the contribution of protein domains to the degradation of mNRE was investigated, which showed that the transmembrane and regulatory domain played a role in the degradation of mNRE by macroautophagy and the proteasome respectively. In contrast the C-terminal catalytic domain was not involved in both degradation pathways of mNRE. These findings showed for the first time that the degradation pathways in controlling mNRE quantity and may provide further insight into structure and regulation of mNRE.
Mol Biol Rep 2012 Jun
PMID:Degradation of mouse NTE-related esterase by macroautophagy and the proteasome. 2230 96

Phospholipase A1 (PLA1) has been described in the infective stages of Trypanosoma cruzi as a membrane-bound/secreted enzyme that significantly modified host cell lipid profile with generation of second lipid messengers and concomitant activation of protein kinase C. In the present work we determined higher levels of PLA1 expression in the infective amastigotes and trypomastigotes than in the non-infective epimastigotes of lethal RA strain. In addition, we found similar expression patterns but distinct PLA1 activity levels in bloodstream trypomastigotes from Cvd and RA (lethal) and K98 (non-lethal) T. cruzi strains, obtained at their corresponding parasitemia peaks. This fact was likely due to the presence of different levels of anti-T. cruzi PLA1 antibodies in sera of infected mice, that modulated the enzyme activity. Moreover, these antibodies significantly reduced in vitro parasite invasion indicating the participation of T. cruzi PLA1 in the early events of parasite-host cell interaction. We also demonstrated the presence of lysophospholipase activity in live infective stages that could account for self-protection against the toxic lysophospholipids generated by T. cruzi PLA1 action. At the genome level, we identified at least eight putative genes that codify for T. cruzi PLA1 with high amino acid sequence variability in their amino and carboxy-terminal regions; a putative PLA1 selected gene was cloned and expressed as a recombinant protein that possessed PLA1 activity. Collectively, the results presented here point out at T. cruzi PLA1 as a novel virulence factor implicated in parasite invasion.
Mol Biochem Parasitol 2013 Feb
PMID:Phospholipase A1: a novel virulence factor in Trypanosoma cruzi. 2327 96


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