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Query: UNIPROT:P06889 (Mol)
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Both Pseudomonas aeruginosa and Pseudomonas fluorescens secrete a lipase into the extracellular medium. Unlike the lipase of P. aeruginosa, the lipase produced by P. fluorescens does not contain any N-terminal signal sequence. We show that the P. fluorescens lipase is secreted through the signal peptide-independent pathway of the alkaline protease that we previously identified in P. aeruginosa. Secretion of this protease (AprA) is dependent on the presence of three genes located adjacent to the aprA gene, aprD, aprE and aprF. The three secretion functions permit an efficient secretion of P. fluorescens lipase. Inactivation of one of them (AprE) prevented this secretion. In Escherichia coli, the three proteins AprD, AprE, AprF are necessary and sufficient for efficient secretion of lipase to the extracellular medium. The secretion signal is located within the C-terminal part of the lipase sequence and can promote efficient secretion of a passenger protein. Thus the P. fluorescens lipase secretion system belongs to the group of the three-component bacterial ABC-exporter systems.
Mol Microbiol 1994 Mar
PMID:The Pseudomonas fluorescens lipase has a C-terminal secretion signal and is secreted by a three-component bacterial ABC-exporter system. 802 81

Phospholipase C (PLC) activity and its response to stimulation by bile acids was assayed in cellular extracts from 16 primary human colon tumors of various Duke's stages and paired adjacent normal mucosal samples. In the absence of bile acid, there was negligible degradation of phosphatidylinositol (PI) 1-stearoyl-2-[14C]-arachiodonoyl by tumor or normal tissue, but the addition of deoxycholic acid (DCA) or taurocholic acid (TCA) resulted in concentration-dependent and time-dependent stimulation of diacylglycerol (DAG) formation at optimal concentrations of 2 mM DCA and 4 mM TCA. Triton X-100 (0.125-1.0%) inhibited rather than enhanced the PI-degrading activity of these extracts, indicating that the stimulatory effects of DCA and TCA were not simply due to a detergent effect. Under the same assay conditions there was only a small amount of labeled monoacylglycerol or free arachidonic acid produced by extracts incubated in the absence or presence of DCA or TCA. No major differences in DAG production from PI were seen between paired samples of normal colon mucosa and primary colon tumors, in assays done in the presence of 2 mM TCA. Extracts from tumors in the distal part of the colon had higher activity than those from the proximal colon. This was also true for the extent of release of free arachidonic acid from labeled PI. Under the same conditions, labeled phosphatidylcholine or phosphatidylethanolamine did not serve as substrates for the colon mucosa or tumor extracts. Nor was there significant hydrolysis of the labeled DAG (1-stearoyl-2-14C-arachidonoylglycerol) by normal colon mucosa or tumor extracts, in the absence or presence of DCA or TCA. On the other hand, a low level of DAG lipase activity was detected in the presence of Triton X-100. These findings provide the first evidence that normal human colon mucosa and primary colon tumors contain a PI-specific PLC activity that is markedly stimulated by bile acids. Our results also suggest that bile acids may enhance colon carcinogenesis by acting on this enzyme system, thereby influencing signal transduction pathways in the target cells.
Mol Carcinog 1994 Feb
PMID:The effects of bile acids on phospholipase C activity in extracts of normal human colon mucosa and primary colon tumors. 814 13

The synaptic plasma membrane (SPM) and cytosol fractions from cerebral cortex of adult (4-mo-old) and aged (27-mo-old) rats were used as a source of phospholipase A2 (PLA2) and phospholipase C (PLC). The activity of PLC acting on [3H-inositol]phosphatidylinositol ([3H]PtdIns) was investigated in the presence of endogenous and 2 mM Ca2+. Arachidonic acid (AA) release was studied in the same conditions, using 1-stearoyl-[2-14C]arachidonyl-sn-glycerophosphoinositol ([14C]PtdIns) as a substrate. In the presence of endogenous Ca2+ (i.e., no added Ca2+) SPM-bound PLC and PLA2 or diacylglycerol (DAG) lipase of aged brain exert significantly higher activity in degradation of PtdIns as compared to their activities in adult brain. Moreover, these enzymes of aged brain are less or not further activated by 2 mM Ca2+, contrary to the enzymes isolated from adult brain. The activity of cytosolic enzymes involved in degradation [3H]PtdIns and [14C]PtdIns and their regulation by Ca2+ ions are not significantly changed in senescent cerebral cortex as compared to the adult. The intracellular calcium concentration ([Ca2+]i), measured with fura-2, is lower in aged brain compared to adult brain, which may suggest the modification in Ca2+ ion redistribution in aged brain and probably its higher concentration in membranes. These results indicate that aging modifies significantly the activity of membrane-bound, Ca(2+)-dependent phospholipase(s) degrading PtdIns, which may be connected with alteration of Ca2+ ion redistribution and may influence the formation and accumulation of very potent lipid messengers as diacylglycerol, lysophospholipid, and arachidonic acid, known to be involved in neurotransmission processes.
Mol Chem Neuropathol 1994 Jan
PMID:Aging modulates calcium-dependent phosphatidylinositol degradation by cerebral cortex synaptic plasma membrane phospholipases. 817 75

Pancreatic lipase (EC 3.1.1.3) plays a key role in dietary fat digestion by converting triacylglycerols into 2-monoacylglycerols and free fatty acids in the intestine. Although the crystallographic structures of the human pancreatic lipase and of a human lipase-porcine colipase complex have been solved, no refined structure of pancreatic lipase has yet been published. The crystal structure of the horse enzyme was solved by the molecular replacement method from the model of the human pancreatic lipase and subsequently refined to 2.3 A resolution. The final model contains two molecules of 449 amino acid residues each in the asymmetric unit, 705 well-defined water molecules and two calcium ions. The two molecules in the asymmetric unit of the orthorhombic crystals are related by a 2-fold non-crystallographic symmetry axis as in the case of the human lipase. However, the association between the two molecules in their respective crystal forms is different. The overall molecular structure of the horse lipase is very similar to that of the human enzyme. The horse lipase is made up of two well-defined domains. The N-terminal domain which bears the active centre has a typical alpha/beta hydrolase fold topology. The C-terminal domain which is devoted to colipase binding has a beta-sheet sandwich topology. Comparison of equivalent C alpha atom positions between the final model of the horse lipase and the human lipase structure shows only slight differences which are mainly located in the C-terminal domain. The horse enzyme possesses the common features of the known mammalian and microbial lipases, in particular the "flap" covering the catalytic triad. In addition to more precise information concerning these features, the elucidation of the horse lipase crystal structure allowed us to better understand the structural basis of the kinetic behaviour of pancreatic lipases towards a soluble substrate, p-nitrophenyl acetate, and the different sensitivity of these enzymes towards limited proteolysis.
J Mol Biol 1994 May 20
PMID:Horse pancreatic lipase. The crystal structure refined at 2.3 A resolution. 818 45

Single crystals of the lipase from Bacillus subtilis have been obtained using a mixture of polyethylene glycol 4000 and sodium sulphate solution as the precipitant. The crystals grow at room temperature in two to three weeks in the presence of n-octyl-beta-D-glucoside. They belong to the monoclinic space group C2 with a = 121.20 A, b = 93.19 A, c = 80.96 A, and beta = 110.67 degrees, with four protein molecules per asymmetric unit. The crystals diffract to at least 2.5 A resolution and are suitable for an X-ray structure analysis.
J Mol Biol 1994 May 20
PMID:Crystallization and preliminary X-ray analysis of a lipase from Bacillus subtilis. 818 56

In order to investigate the effects of two contraceptive steroids given orally, which contain ethinyl estradiol in combination with different types and doses of progestins, on plasma lipoprotein metabolism, rat groups named according to progestin components were designated as short-and long-term groups of norethisterone acetate and levonorgestrel at low-and high-doses. At the end of the experiments, plasma triglyceride, phospholipid, apolipoprotein A1 and B, LDL-, HDL-, HDL2- and HDL3-cholesterol levels and hepatic lipase activity were measured. When compared to controls, phospholipid and LDL-cholesterol were increased in all groups; triglyceride levels were also increased in all short-term groups, but only in low-dose norethisterone and high-dose levonorgestrel of long-term groups. HDL- and HDL3- cholesterol were decreased in all groups, except in low-dose levonorgestrel groups, but HDL2-cholesterol were lower only at high doses and long period. In short-term, an increase in apolipoprotein A1 levels was significantly important at high doses; in long-term apolipoprotein A1 was increased at low doses, while decreased at high doses. Apolipoprotein B was elevated only in long-term high dose of norethisterone acetate group. Hepatic lipase activity was increased in long-term high-dose of levonorgestrel group, whereas decreased in all other groups. In conclusion, the data presented was interpreted that the effects of these combinations used in the study on plasma lipoprotein metabolism may be related to the changes observed in hepatic lipase activity.
Biochem Mol Biol Int 1993 Jun
PMID:The effect of contraceptive steroids on plasma lipoprotein metabolism in female rats (II). 836 6

Pseudomonas glumae PG1 is able to secrete lipase into the extracellular medium. The lipase is produced as a precursor protein, with an N-terminal signal sequence. A second open reading frame (ORF) was found immediately downstream of the lipase structural gene, lipA, a situation found for the lipases of some other Pseudomonas species. Inactivation of this ORF resulted in a lipase-negative phenotype, indicating its importance in the production of active extracellular lipase. The ORF, lipB, potentially encodes a protein of 353-amino-acid residues, having a hydrophobic N-terminal (amino acids 1 to 90) and a hydrophilic C-terminal part. As a first step in determining the role of LipB, its subcellular location was determined. The protein was found to fractionate with the inner membranes. The expression of fusions of lipB fragments with phoA revealed an N(in)-C(out) topology for the LipB protein, which was confirmed by protease accessibility studies on EDTA-permeabilized cells and on inverted inner membrane vesicles. These and other results indicate that most of the LipB polypeptide is located in the periplasm and anchored to the inner membrane by an N-terminal transmembrane helix, located between amino acids 19 and 40.
Mol Microbiol 1993 Aug
PMID:An accessory gene, lipB, required for the production of active Pseudomonas glumae lipase. 841 4

The LipB protein of Pseudomonas glumae is essential for the production of active extracellular lipase encoded by the lipA gene. When lipase is overproduced in P. glumae in the absence of a functional lipB gene, the enzyme accumulates intracellularly in an inactive conformation. Heterologous expression of the lipase in Pseudomonas aeruginosa, Bacillus subtilis and Escherichia coli indicated that LipB is not directly involved in the translocation of the lipase across the inner or outer membrane. However, the presence of LipB was essential for obtaining active lipase and had a profound influence on the stability of the protein to proteolytic degradation. Inactive lipase, produced in the absence of LipB could be activated in vitro by unfolding and refolding, which demonstrates that LipB activity is not responsible for an essential covalent modification of the enzyme. We propose that LipB is a lipase-specific foldase. Furthermore, proper folding of the lipase in the periplasm appears to be essential for Xcp-mediated translocation across the outer membrane.
Mol Microbiol 1993 Aug
PMID:Role of the lipB gene product in the folding of the secreted lipase of Pseudomonas glumae. 841 5

A lipase from the fungus Geotrichum candidum is one of only three interfacially activated lipases whose structures have been reported to date. We have previously reported the partially refined 2.2 A structure of this enzyme. We have subsequently extended the resolution and here report the fully refined 1.8 A structure of this lipase. The structure observed in the crystal is apparently not the lipolytic conformation, as the active site is not accessible from the surface of the molecule. A single large cavity is found in the interior of the molecule and extends from the catalytic Ser to two surface helices, suggesting that this face may be the region that interacts with the lipid interface. The mobility of local segments on this face is indicated by temperature factors larger than elsewhere in the molecule and by the observation of several residues whose side-chains are discretely disordered. These observations strongly suggest that this portion of the molecule is involved in interfacial and substrate binding, but the exact nature of the conformational changes induced by binding to the lipid interface can not be determined.
J Mol Biol 1993 Mar 20
PMID:1.8 A refined structure of the lipase from Geotrichum candidum. 846 65

This study evaluated fat mobilization as related to gluconeogenesis in two age groups of hibernating golden-mantled ground squirrels (Spermophilus lateralis). Our experimental group consisted of a total of 16 male and 15 female squirrels. Plasma samples were collected from selected animals being killed weekly from January to March, and the concentration of triglycerides, glycerol (GY), free fatty acids (FFA), total cholesterol, lipase activity, glucose, and insulin, were determined by biochemical assays and radioimmunoassay. Our results showed a mean FFA/GY ratio of five, which was higher than the predicted value of three, suggesting a significant depletion of GY and an enhanced rate of gluconeogenesis via GY to maintain glucose homeostasis in the hibernating animals. The factor of age did not significantly affect plasma lipid components. However, in the male group, plasma glucose levels were significantly higher for adults than for juveniles. Overall, females had significantly higher plasma glucose levels than males (150 +/- 11 vs. 110 +/- 8 mg%, P < 0.05). In the adult group, a gender influence was also seen on plasma insulin levels, with females' being higher than males' (66 +/- 13 vs. 25 +/- 3 microIU/ml, P < 0.01). We suggest that during hibernation, female squirrels may have a higher rate of lipolysis and gluconeogenesis along with a lower glucose utilization than their male counterparts. Additionally, adult females may exhibit a higher peripheral insulin resistance during hibernation than adult males, a possibility which merits further study.
Comp Biochem Physiol B Biochem Mol Biol 1995 Aug
PMID:Changes in various plasma lipid components, glucose, and insulin in Spermophilus lateralis during hibernation. 857 26


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