Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of L-TYR on rat uterine cytosol estradiol and progesterone receptor contents was studied. The rats were divided into 4 groups: proestrus, estrus, metestrus and diestrus. One horn of each uterus was injected with L-TYR (2 mmol/L, 0.1 ml), while the other with 0.1 ml 0.9% NaCl serving as control. The mole concentration of receptor was calculated with RRA and cytosol receptor content was expressed as fmol/mg protein. It was shown that L-TYR decreased significantly the uterine estradiol and progesterone receptors in proestrus, estrus and diestrus phases of the estrus cycle, but without effect on metestrus. This was most probably due to competitive combination of TYR with some functional groups of the estradiol receptor because of similar chemical conformation of TYR to estradiol. Threonine could also decrease, to some extent, the uterine cytosol progesterone receptor content at estrus and dioestrus phases. Serine had no effect on the contents of uterine cytosol either estradiol or progesterone receptor in normal and ovariectomized rats. The present observation indicates that L-TYR appears to affect the synthesis of the cytosol estradiol and progesterone receptor in the rat uterus independent, however, of endogenous ovarian sex hormones, since the effect is still present in the ovariectomized animals.
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PMID:[Effect of L-TYR on the uterine cytosol estradiol and progesterone receptors in rat]. 875 96

A search for tissue kallikreins in lower vertebrates resulted in the discovery of three novel kallikreins. Tissue kallikrein was isolated from the salivary gland of the Eastern Atlantic mole, Scalopus aquaticus, and the pancreas of the Southern frog, Rana berlandieri. A prokallikrein was identified in skeletal muscle of the black sea bass, Centropristis striata. These enzymes range in molecular mass from 27 to 36 kDa and are acidic proteins with pIs between 4.2 and 5.3. Bass prokallikrein was activated by trypsin cleavage. These novel kallikreins were compared with human and rat tissue kallikreins in regard to immunoreactivity, molecular weight, isoelectric point, extinction coefficient, susceptibility to serine proteinase inhibitors and their ability to cleave low molecular weight dog kininogen to release kinin peptides.
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PMID:Tissue kallikreins in evolutionarily diverse vertebrates. 879 77

Myosin II heavy chain (MHC)-specific protein kinase C (MHC-PKC) isolated from the ameba, Dictyostelium discoideum, regulates myosin II assembly and localization in response to the chemoattractant cAMP. cAMP stimulation of Dictyostelium cells leads to translocation of MHC-PKC from the cytosol to the membrane fraction, as well as causing an increase in both MHC-PKC phosphorylation and its kinase activity. MHC-PKC undergoes autophosphorylation with each mole of kinase incorporating about 20 mol of phosphate. The MHC-PKC autophosphorylation sites are thought to be located within a domain at the COOH-terminal region of MHC-PKC that contains a cluster of 21 serine and threonine residues. Here we report that deletion of this domain abolished the ability of the enzyme to undergo autophosphorylation in vitro. Furthermore, after this deletion, cAMP-dependent autophosphorylation of MHC-PKC as well as cAMP-dependent increases in kinase activity and subcellular localization were also abolished. These results provide evidence for the role of autophosphorylation in the regulation of MHC-PKC and indicate that this MHC-PKC autophosphorylation is required for the kinase activation in response to cAMP and for subcellular localization.
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PMID:Autophosphorylation of Dictyostelium myosin II heavy chain-specific protein kinase C is required for its activation and membrane dissociation. 899 70

Erythrocyte agglutination by lectins from Allium sativum was inhibited only by mannose of the sugars tested. However, asialofetuin was more effective inhibitor of agglutination as compared to mannose. This led to the use of an asialofetuin-silica affinity column to isolate agglutinins of 110 and 25 kDa (ASA110 and ASA25). While ASA25 is a dimeric protein comprising of subunits of 12.5 and 13.0 kDa, ASA110 is a glycoprotein of two identical subunits of 47 kDa. ASA110 revealed to have a high content of aspartic acid, glycine, leucine and serine but low content of cysteine and methionine. It contains 14 residues of neutral sugars in addition to 43 residues of hexosamines per mole of lectin and requires metal ions for its functional conformation. Serological cross-reactions with other species showed some common epitopes of ASA110 and ASA25 present in A. porrum, A. ascalonicum, Narcissus alba, PHA and Con A but not in A. cepa. ASA110 with CHO cells indicated it to be weakly cytotoxic with LD50 of 160 microg/ml.
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PMID:A new high molecular weight agglutinin from garlic (Allium sativum). 904 16

Csk is a protein tyrosine kinase that phosphorylates other protein tyrosine kinases of the Src family and down-regulates their activities. It is not known how Csk is regulated. We investigated the possibility that Csk is regulated through phosphorylation by examining if Csk can serve as an in vitro substrate for a panel of protein kinases. We found that Csk was phosphorylated by the cAMP-dependent protein kinase (PKA), but not by protein kinase C, Src, or the fibroblast growth factor receptor kinase. Csk phosphorylation in vitro by PKA is on a serine residue(s) and can reach a stoichiometry of approximately 0.6 mol phosphate per mole of enzyme. Furthermore, incubation with PKA in the presence of ATP and magnesium ion results in a time-dependent decrease in Csk kinase activity. A six-fold decrease in Csk activity (expressed as Vmax/Km ratio) was achieved due to a threefold increase in its Km and a twofold decrease in its Vmax value within 1 h of incubation with the catalytic subunit of PKA and ATP-Mg. Both phosphorylation and inactivation by PKA were blocked by a PKA-specific inhibitor. Csk mutants with a deleted SH2 or SH3 domain retained their ability to be phosphorylated and inactivated by PKA, indicating that the phosphorylation site is located within the catalytic domain. These studies suggest that the cAMP-dependent protein kinase can regulate Csk activity.
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PMID:Csk phosphorylation and inactivation in vitro by the cAMP-dependent protein kinase. 922 30

The binding of Src to phospholipid membranes requires both hydrophobic insertion of its myristate into the hydrocarbon interior of the membrane and nonspecific electrostatic interaction of its N-terminal cluster of basic residues with acidic phospholipids. We provide a theoretical description of the electrostatic partitioning of Src onto phospholipid membranes. Specifically, we use molecular models to represent a nonmyristoylated peptide corresponding to residues 2-19 of Src [nonmyr-Src(2-19); GSSKSKPKDPSQRRRSLE-NH2] and a phospholipid bilayer, calculate the electrostatic interaction by solving the nonlinear Poisson-Boltzmann equation, and predict the molar partition coefficient using statistical thermodynamics. The theoretical predictions agree with experimental data obtained by measuring the partitioning of nonmyr-Src(2-19) onto phospholipid vesicles: membrane binding increases as the mole percent of acidic lipid in the vesicles is increased, the ionic strength of the solution is decreased, or the net positive charge of the peptide is increased. The theoretical model also correctly predicts the measured partitioning of the myristoylated peptide, myr-Src(2-19); for example, adding 33% acidic lipid to electrically neutral vesicles increases the partitioning of myr-Src(2-19) 100-fold. Phosphorylating either serine 12 (by protein kinase C) or serine 17 (by cAMP-dependent protein kinase) decreases the partitioning of myr-Src(2-19) onto vesicles containing acidic lipid 10-fold. We investigated the effect of phosphorylation on the localization of Src to biological membranes by expressing fusion constructs of Src's N terminus with a soluble carrier protein in COS-1 cells; phosphorylation produces a small shift in the distribution of the Src chimeras from the plasma membrane to the cytosol.
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PMID:Electrostatics and the membrane association of Src: theory and experiment. 948 61

A cysteine protease inhibitor exhibiting antifungal activity from pearl millet seeds has been purified to homogeneity by ammonium sulphate precipitation and chromatographic procedures involving CM- sephadex and SP-sepharose cation exchange columns. The molecular characterization has revealed its molecular mass as 24 kD and isoelectric point 9.8. The amino acid composition data shows presence of high content of serine and glycine (34 residues/mole) and absence of tryptophan. The inhibitor exhibits potent antifungal activity against Trichoderma reesei, a dead wood fungus with minimum inhibitory dose to inhibit mycelial growth or spore germination is as low as 1 microgram/ml (250 ng/disc). In addition to Trichoderma reesei, the antifungal activity is observed against some important phytopathogenic fungi, namely, Claviceps, Helminthosporium, Curvularia, Alternaria and Fusarium species. To the best of our knowledge, a cysteine protease inhibitor as an antifungal protein is reported for the first time from a plant system.
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PMID:Cysteine protease inhibitor from pearl millet: a new class of antifungal protein. 961 Mar 68

Cytosolic phospholipase A2 (cPLA2) catalyzes the selective release of arachidonic acid from the sn-2 position of phospholipids and is believed to play a key cellular role in the generation of arachidonic acid. When assaying the human recombinant cPLA2 using membranes isolated from [3H]arachidonate-labeled U937 cells as substrate, 3,3-Dimethyl-6-(3-lauroylureido)-7-oxo-4-thia-1-azabicyclo[3,2,0] heptane-2-carboxylic acid (1) was found to inhibit the enzyme in a dose-dependent manner (IC50 = 72 microM). This beta-lactam did not inhibit other phospholipases, including the human nonpancreatic secreted phospholipase A2. The inhibition of cPLA2 was found not to be time-dependent. This, along with the observation that the degradation of the inhibitor was not catalyzed by the enzyme, demonstrates that the inhibition does not result from the formation of an acyl-enzyme intermediate with the active site serine residue. Moreover, the ring-opened form of 1 is also able to inhibit cPLA2 with near-equal potency. To further characterize the mechanism of inhibition, an assay in which the enzyme is bound to vesicles of 1,2-dimyristoyl-sn-glycero-3-phosphomethanol containing 6-10 mole percent of 1-palmitoyl-2-[1-14C]-arachidonoyl-sn-glycero-3-phosphocholine was employed. With this substrate system, the dose-dependent inhibition was defined by kinetic equations describing competitive inhibition at the lipid/water interface. The apparent dissociation constant for the inhibitor bound to the enzyme at the interface (KI*app) was determined to be 0.5 +/- 0.1 mole% versus an apparent dissociation constant for the arachidonate-containing phospholipid of 0.4 +/- 0.1 mole%. Thus, 1 represents a novel structural class of inhibitors of cPLA2 which partitions into the phospholipid bilayer and competes with the phospholipid substrate for the active site.
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PMID:A beta-lactam inhibitor of cytosolic phospholipase A2 which acts in a competitive, reversible manner at the lipid/water interface. 962 37

The roles of chymase in acute allergic responses are not clear, despite the relative abundance of this serine proteinase in the secretory granules of human mast cells. We have isolated chymase to high purity from human skin tissue by heparin-agarose affinity chromatography and Sephacryl S-200 gel filtration procedures, and have investigated the ability of human mast cell chymase to stimulate cell accumulation following injection into laboratory animals. Injection of chymase provoked marked neutrophilia and eosinophilia in the skin of Dunkin Hartley guinea-pigs. Compared with saline injected control animals, there were some 60 fold more neutrophils and 12 fold more eosinophils present at the injection site. Following injection of chymase into the peritoneum of BALB/c mice, there were up to 700 fold more neutrophils. 21 fold more eosinophils, 19 fold more lymphocytes and 7 fold more macrophages recovered than from saline injected controls at 16 h. Doses of chymase as low as 5 ng (1.7 x 10(-13) mole) stimulated an inflammatory infiltrate, and significant neutrophilia was elicited within 3 h. The chymase induced cell accumulation in both the guinea-pig and mouse models was dependent on an intact catalytic site, being reduced by co-injection of proteinase inhibitors or heat inactivation of the enzyme. Co-injection of histamine or heparin significantly reduced the chymase induced neutrophil accumulation, whereas neither histamine nor heparin by themselves had any effect on the accumulation of nucleated cells. No synergistic or antagonist interactions between chymase and tryptase were observed when these two major mast cell proteinases were co-injected into the mouse peritoneum. Our findings suggest that chymase may provide an potent stimulus for inflammatory cell recruitment following mast cell activation.
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PMID:Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo. 988 78

The binding of L-serine to phosphoglycerate dehydrogenase from Escherichia coli displays elements of both positive and negative cooperativity. At pH 7.5, approximately 2 mol of serine are bound per mole of tetrameric enzyme. A substantial degree of positive cooperativity is seen for the binding of the second ligand, but the binding of the third and fourth ligand display substantial negative cooperativity. The data indicate a state of approximately 50% inhibition when only one serine is bound and approximately 80-90% inhibition when two serines are bound. This is consistent with the tethered domain hypothesis that has been presented previously. Comparison of the data derived directly from binding stoichiometry to the binding constants determined from the best fit to the Adair equation, produce a close agreement, and reinforce the general validity of the derived binding constants. The data also support the conclusion that the positive cooperativity between the binding to the first and second site involves binding sites at opposite interfaces over 110 A apart. Thus, an order of binding can be envisioned where the binding of the first ligand initiates a conformational transition that allows the second ligand to bind with much higher affinity at the opposite interface. This is followed by the third ligand, which binds with lesser affinity to one of the two already occupied interfaces, and in so doing, completes a global conformational transition that produces maximum inhibition of activity and an even lower affinity for the fourth ligand, excluding it completely. Thus, maximal inhibition is accomplished with less than maximal occupancy of effector sites through a mechanism that displays strong elements of both positive and negative cooperativity.
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PMID:The relationship between effector binding and inhibition of activity in D-3-phosphoglycerate dehydrogenase. 1059 55


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