Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of Adriamycin on mitochondria of the rat heart, liver, and Ehrlich ascites tumor mitochondria has been evaluated. The results may be summarized as follows: Adriamycin reduces both ADP- and FCCP-stimulated respiration, inhibits oxidative phosphorylation, decreases mitochondrial ATP-ase activity, and affects the redox state of respiratory carriers. These alterations are common to all types of mitochondria tested with almost similar patterns. However, the severe cardiotoxicity of the drug cannot be ascribed only to an effect on mitochondrial energy-yielding processes. The addition of hexokinase to phosphorylating heart mitochondria does not increase the sensitivity of succinate oxidation to Adriamycin. Experiments to determine the site of action were not able to detect a specific point of attack. It is conceivable, therefore, that the modifications induced by Adriamycin on the functional parameters of mitochondria may be ascribed to alterations of the physical state of some components of the inner mitochondrial membrane, e.g., lipids, which regulate the kinetic properties of the membrane-associated enzymes.
Exp Mol Pathol 1987 Feb
PMID:Effect of adriamycin on electron transport in rat heart, liver, and tumor mitochondria. 287 39

The acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) is a potent inhibitor of human cytomegalovirus in vitro and in vivo. In order to investigate the phosphorylation of DHPG to the monophosphate and identify the enzyme responsible, attempts were made to isolate DHPG kinase from calf thymus and from human cytomegalovirus-infected lung cells. From calf thymus, a mitochondrial deoxyguanosine kinase was partially purified which co-migrated with DHPG phosphorylating activity on DEAE-cellulose, and had the same mobility by electrophoresis. DHPG triphosphate and DHPG kinase were elevated in cytomegalovirus-infected cells, but not enough enzyme activity was recovered to identify the kinase. However, DHPG was found to inhibit a cytosol deoxyguanosine kinase induced in these infected cells. The role of mitochondrial and cytosol deoxyguanosine kinases is discussed relative to the anti-cytomegalovirus activity of DHPG.
Mol Cell Biochem 1985 Nov
PMID:Interaction of 9-(1,3-dihydroxy-2-propoxymethyl)guanine with cytosol and mitochondrial deoxyguanosine kinases: possible role in anti-cytomegalovirus activity. 300 5

Three benzenoid ansamycin antibiotics (herbimycin, macbecin, and geldanamycin) were found to reduce the intracellular phosphorylation of p60src at a permissive temperature (33 degrees C) in a rat kidney cell line infected with a temperature-sensitive mutant of Rous sarcoma virus. This effect was accompanied by morphological changes from the transformed to the normal phenotype. The filamentous staining pattern of actin fibers was observed in the cells treated with these antibiotics at 33 degrees C. Removal of the antibiotics allowed the cells to revert to the transformed morphology. Ansamitocin, another benzenoid ansamycin, and naphthalenoid ansamycins such as streptovaricin and rifamycins did not show this effect. Pulse-labeling of the antibiotic-treated cultures with 32Pi showed a marked reduction of 32P radioactivity incorporated into p60src. A parallel experiment with [35S]methionine showed that synthesis of p60src was slightly inhibited. The immune complex prepared by mixing the herbimycin-treated cell extracts with antibody against p60src was inactive in vitro in phosphorylating the complex itself. On the contrary, the immune complex derived from untreated cells was active in vitro even in the presence of the antibiotics. These results suggest that benzoquinonoid ansamycins have no direct effect on src kinase but destroy its intracellular environment, resulting in an irreversible alteration of p60src and loss of catalytic activity.
Mol Cell Biol 1986 Jun
PMID:Phenotypic change from transformed to normal induced by benzoquinonoid ansamycins accompanies inactivation of p60src in rat kidney cells infected with Rous sarcoma virus. 302 21

Human SY5Y neuroblastoma cells which were differentiated in culture by treatment with 7S murine nerve growth factor for 5 weeks and selection with aphidicolin (L. Jensen, Dev. Biol. 120:56-64, 1987) demonstrated a considerably slower rate of removal of DNA adducts of benzo[a]pyrene, benzo[a]pyrenediolepoxide, and N7-methylguanine than did undifferentiated mitotic cells. A dramatic decline in unscheduled DNA synthesis induced by UV radiation was similarly observed. DNA polymerase beta and uracil DNA glycosylase were unchanged after differentiation, DNA polymerase alpha and DNA methylase decreased roughly threefold, and total apurinic-apyrimidinic endonuclease activity increased roughly threefold after treatment.
Mol Cell Biol 1988 Sep
PMID:A reduced rate of bulky DNA adduct removal is coincident with differentiation of human neuroblastoma cells induced by nerve growth factor. 314 94

We have employed sera from patients with autoimmune disease to characterize the nuclear SS-B/La antigen in uninfected and adenovirus-infected KB cells. A 45,000-dalton phosphorylated polypeptide was specifically precipitated with anti-SS-B sera, and the level of phosphorylation was increased after infection. The increased phosphorylation appears to occur at the same amino acid residues phosphorylated in uninfected cells and results from increased phosphorylating activity rather than from altered enzyme specificity. A competition experiment between infected and uninfected cell extracts indicates that the antigen in the infected cell binds more strongly to SS-B/La antibodies. Fragments of adenovirus-induced virus-associated RNA as well as intact molecules complex with SS-B/La antigen and are immune precipitated with autoimmune sera.
Mol Cell Biol 1983 Jul
PMID:Characterization of a phosphoprotein associated with the SS-B/La nuclear antigen in adenovirus-infected and uninfected KB cells. 619 14

Hexokinase (ATP: hexose 6-phosphotransferase, E.C.2.7.1.1) and phosphofructokinase (ATP:fructose-6-phosphate 1-phosphotransferase, E.C.2.7.1.11), two key regulatory enzymes of the glycolytic pathway in vertebrate cells, have been isolated and partially purified from Trypanosoma (Schizotrypanum) cruzi epimastigotes. Both enzymes are associated with particles sedimentable at 105 000 X gav for 1 h and have a high degree of latency; they can be solubilized by sonication. Hexokinase catalyses the phosphorylation of a series of monosaccharides at the following relative rates: D-glucose (100) congruent to D-fructose (97) greater than 2-deoxy-D-glucose (72) congruent to mannose (69) greater than 2-amino-D-glucose (63) greater than 3-O-methyl-D-glucose (21). Very little or no phosphorylating activity was found for D-galactose, N-acetyl-2-amino-D-glucose or 1-alpha-methyl-D-glucose. D-Glucose phosphorylation at fixed ATP concentration follows simple Michaelis-Menten kinetics with Km = 40 microM and Vmax = 440 nmol min-1 mg-1 protein. D-Mannose, 2-deoxy-D-glucose and N-acetyl-2-amino-D-glucose act as competitive inhibitors of glucose phosphorylation, suggesting a single kinase. Mg2+-ATP is the preferred phosphoryl donor, ITP and GTP being much less effective. T. cruzi hexokinase is not inhibited by D-glucose 6-phosphate, or by any of the following compounds (2 mM):D-fructose 6-phosphate, D-fructose 1,6-diphosphate, D-glucose 1,6-diphosphate, phosphoenol pyruvate, L-malate and citrate. Phosphofructokinase displays simple Michaelis-Menten kinetics with no evidence of sigmoidicity with respect to D-fructose 6-phosphate at all ATP concentrations tested, giving a Km of 1.31 mM and Vmax = 400 nmol min-1 mg-1 protein at optimal ATP levels. With respect to ATP, the enzyme exhibits Michaelis-Menten kinetics at low concentration (less than 1 mM) of the substrate (Km = 40 microM at 5 mM MgCl2, pH 7.4). A moderate inhibition is observed at high ATP levels (70% of maximal activity at 2 mM). GTP can substitute for ATP as the phosphoryl donor (Km = 79 microM under the same conditions), but produces only very small inhibitory effects at high concentrations. 5'-AMP activates the enzyme by decreasing its Km with respect to D-fructose 6-phosphate without affecting Vm. Other well-known regulators of the activity of this enzyme in procaryote and vertebrate systems such as citrate, phosphoenol pyruvate, ammonium and phosphate ions have no effect in T. cruzi.
Mol Biochem Parasitol 1984 Apr
PMID:Regulation of energy metabolism in Trypanosoma (Schizotrypanum) cruzi epimastigotes. I. Hexokinase and phosphofructokinase. 623 52

The biosynthesis of phytic acid is known to be catalyzed by enzymes causing a stepwise phosphorylation of myo-inositol or 1L-myo-inositol 1-phosphate with adenosine triphosphate as phosphate donor. The kinase responsible for these phosphorylations in Lemna gibba were purified by affinity chromatography on a Sepharose gel carrying myo-inositol 2-phosphate at the binding site. Three fractions with enzymatic activity could be identified; in the first one, we find myo-inositol kinase (EC 2.7.1.64) phosphorylating myo-inositol to 1L-myo-inositol 1-phosphate; the second one brings about the phosphorylation of myo-inositol trisphosphate to phytic acid; the third one phosphorylates myo-inositol 1-phosphate to a myo-inositol trisphosphate. An enzyme oxidizing 1L-myo-inositol 1-phosphate to an uronic acid derivative is found in the first two fractions. In the presence of ATP, Mg2+, Mn2+, and the second and the third enzyme fractions in an appropraite mixture, 1L-myo-inositol 1-phosphate can be phosphorylated to phytic acid. The structure of the trisphosphate acting as an intermediate is not yet known.
Mol Cell Biochem 1980 May 07
PMID:The enzymes involved in the synthesis of phytic acid in Lemna gibba (studies on the biosynthesis of cyclitols, XL.(1)). 625 22

Three mutant strains, one conditional, of Tetrahymena thermophila were defective in thymidine phosphorylating activity in vivo and in thymidine kinase activity in vitro. Nucleoside phosphotransferase activity in mutant cell extracts approached wild-type levels, suggesting that thymidine kinase is responsible for most, if not all, thymidine phosphorylation in vivo. Thymidine kinase activity in extracts of the conditional mutant strain was deficient when the cells were grown or assayed or both at the permissive temperature, implying a structural enzyme defect. Analysis of the reaction products from in vitro assays with partially purified enzymes showed that phosphorylation by thymidine kinase and nucleoside phosphotransferase occurred at the 5' position. Genetic analyses showed that the mutant phenotype was recessive and that mutations in each of the three mutant strains did not complement, suggesting allelism.
Mol Cell Biol 1982 Aug
PMID:Mutant strains of Tetrahymena thermophila defective in thymidine kinase activity: biochemical and genetic characterization. 629 Aug 73

Protein kinase activities were measured in Rous sarcoma virus-infected baby hamster kidney (BHK) cells that express v-src (BHK [v-src]) and compared with those of revertant and control BHK cells. We observed about a fivefold-higher tyrosine phosphorylating activity in BHK (v-src) cell extracts, which was due to src but not other cellular tyrosyl kinase activities since preincubation with anti-src serum reduced the activity to control cell levels. The cyclic AMP-dependent protein kinase activity was also altered when v-src was expressed. Resolution of the two cyclic AMP-dependent isozymes from the detergent-soluble fraction of cells revealed that the type I activity was selectively decreased about fivefold in BHK (v-src) cells.
Mol Cell Biol 1984 May
PMID:Tyrosyl and cyclic AMP-dependent protein kinase activities in BHK cells that express viral pp60src. 632 80

Modification of phenylalanyl-tRNA synthetase from E. coli MRE600 by adenosine-5'-trimetaphosphate, phosphorylating analog of ATP was shown to bring about the enzyme inactivation in the reactions of tRNA aminoacylation and ATP-[32P]pyrophosphate exchange. ATP when added in the reaction mixture protects the enzyme against inactivation in both reactions and decreases the level of covalent attachment of the analog. Phenylalanine has no protective effect. tRNA exhibits slight protective effect. Adenosine-5'-trimetaphosphate modifies both types (alpha and beta) of subunits of phenylalanyl-tRNA synthetase which is of alpha 2 beta 2 structure. ATP protects both types of the enzyme subunits against the covalent attachment of the analog. Disposition of the ATP-binding centers in the contact region of the nonequivalent subunits of the enzyme was proposed. The level of covalent attachment of the analog to the enzyme exceeds the number of the enzyme active sites that may be a consequence of the other nucleotide-binding center labeling.
Mol Biol (Mosk)
PMID:[Modification of phenylalanyl-tRNA-synthetase from Escherichia coli MRE600 by adenosine-5'-trimetaphosphate]. 636 20


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