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At least 1,423 records · Page 79Linked to original sources
PubMed1977

Sulphur metabolism in Paracoccus denitrificans. Purification, properties and regulation of cysteinyl-and methionyl-tRNA synthetase.

Cysteinyl- and methionyl-tRNA synthetases (EC 6.11.-) were purified 1200- and 1000-fold, respectively, from sonic extracts of Paracoccus denitrificans strain 8944, and kinetics, substrate specificity and regulatory properties were determined using the ATP-PPi exchange reaction. Both enzymes had pH optima of approx. 8 and were inhibited by sulphydryl-group reagents. Cysteinyl-tRNA synthetase catalysed L-selenocysteine- and alpha-aminobutyric acid-dependent ATP-PPi exchange and methionyl-tRNA synthetase catalysed L-homocysteine-, L-selenomethionine- and norleucine-dependent ATP-PPi exchange. Both enzymes were inhibited by O-acetylserine. Cysteinyl-tRNA synthetase activity was stimulated by methionine and methionyl-tRNA synthetase activity was stimulated by sulphide, cysteine, and cysteic acid.

Adenosine Triphosphate↗
PubMed1991

Structure of the triosephosphate isomerase-phosphoglycolohydroxamate complex: an analogue of the intermediate on the reaction pathway.

The glycolytic enzyme triosephosphate isomerase (TIM) catalyzes the interconversion of the three-carbon sugars dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) at a rate limited by the diffusion of substrate to the enzyme. We have solved the three-dimensional structure of TIM complexed with a reactive intermediate analogue, phosphoglycolohydroxamate (PGH), at 1.9-A resolution and have refined the structure to an R-factor of 18%. Analysis of the refined structure reveals the geometry of the active-site residues and the interactions they make with the inhibitor and, by analogy, the substrates. The structure is consistent with an acid-base mechanism in which the carboxylate of Glu-165 abstracts a proton from carbon while His-95 donates a proton to oxygen to form an enediol (or enediolate) intermediate. The conformation of the bound substrate stereoelectronically favors proton transfer from substrate carbon to the syn orbital of Glu-165. The crystal structure suggests that His-95 is neutral rather than cationic in the ground state and therefore would have to function as an imidazole acid instead of the usual imidazolium. Lys-12 is oriented so as to polarize the substrate oxygens by hydrogen bonding and/or electrostatic interaction, providing stabilization for the charged transition state. Asn-10 may play a similar role.

Amino Acid Sequence↗
PubMed2001

Inhibition of histone deacetylase activity enhances Fas receptor-mediated apoptosis in leukemic lymphoblasts.

We recently reported that butyrate, an inhibitor of histone deacetylases, is capable of inducing Fas-independent apoptosis in the acute lymphoblastic leukemia cell line CCRF-CEM. Here we demonstrate that butyrate enhances Fas-induced apoptosis in this cell line. The application of different histone deacetylase inhibitors revealed that tetra-acetylated histone H4 is associated with the amplifying effect of butyrate on Fas-induced cell death. FasL, Fas, FADD, RIP, caspase-8, caspase-3, Bid, FLIP(S+L), FLASH and FAP-1, proteins known to act within the Fas-apoptosis cascade, showed no changes in their expression levels in cells treated with butyrate compared with untreated cells. Analyses of Fas-oligomerization and Western blotting as well as enzyme activity assays of caspase-2, caspase-3 and caspase-8 suggest that butyrate enhances Fas-induced apoptosis downstream of Fas but upstream of caspase-8 activation. In immunoprecipitation experiments a 37 kD butyrate-regulated protein was detected which specifically interacts with caspase-8.

Apoptosis↗
PubMed1973

The distribution between gamma-glutamylhydrozamate synthetase and L-glutamine-hydroxylamine glutamyltransferase activities in rat tissues. Studies in vitro.

Two common ways of measuring the potential for glutamine synthesis in a tissue are the rates of formation of gamma-glutamylhydroxamate either by synthesis from glutamate (the glutamylhydroxamate synthetase reaction) or by transfer from glutamine (the glutamyltransferase reaction); it has not been established, however, that either reaction is a specific measure of glutamine synthetase. By differential extraction of glutamylhydroxamate synthetase and glutamyltransferase activities from water homogenates of several rat tissues I obtained an extract, rich in glutamylhydroxamate synthetase activity but nearly devoid of glutamyltransferase activity, and a fraction, solubilized by deoxycholate from the pellet, which contained virtually no glutamylhydroxamate synthetase activity but most of the original glutamyltransferase activity. Synthesis of glutamine, quantitatively similar to the gamma-glutamylhydroxamate formed by glutamylhydroxamate synthetase, is catalysed in the water extract but not in the particulate fraction. gamma-Glutamylhydroxamate formation by glutamylhydroxamate synthetase and glutamyltransferase shows discrepant substrate and metal specificities and can be differentially inhibited by l-methionine sulphoximine, phosphate and adenine nucleotides. The concordance between the formation of glutamine and gamma-glutamylhydroxamate by glutamylhydroxamate synthetase but not by glutamyltransferase and the different solubilities of the glutamylhydroxamate synthetase and glutamyltransferase enzyme activities demonstrate that these two activities are not inextricably associated; they therefore cannot be catalysed exclusively by the same protein.

Acyltransferases↗
PubMed1977

Purification and properties of urease from bovine rumen.

Urease (urea amidohydrolase, EC 3.5.1.5) was extracted from the mixed rumen bacterial fraction of bovine rumen contents and purified 60-fold by (NH4)2SO4 precipitation, calcium phosphate-gel adsorption and chromatography on hydroxyapatite. The purified enzyme had maximum activity at pH 8.0. The molecular weight was estimated to be 120000-130000. The Km for urea was 8.3 X 10(-4) M+/-1.7 X 10(-4) M. The maximum velocity was 3.2+/-0.25 mmol of urea hydrolysed/h per mg of protein. The enzyme was stabilized by 50 mM-dithiothreitol. The enzyme was not inhibited by high concentrations of EDTA or phosphate but was inhibited by Mn2+, Mg2+, Ba2+, Hg2+, Cu2+, Zn2+, Cd2+, Ni2+ and Co2+. p-Chloromercuribenzenesulfphonate and N-ethylmaleimide inhibited the enzyme almost completely at 0.1 mM. Hydroxyurea and acetohydroxamate reversibly inhibited the enzyme. Polyacrylamide-gel electrophoresis showed that the mixed rumen bacteria produce ureases which have identical molecular weights and electrophoretic mobility. No multiple forms of urease were detected.

Animals↗
PubMed1996

Iron utilization studies in Citrobacter species.

Seventy-one strains of Citrobacter were screened for iron scavenging mechanisms by biologic and chemical assays. Essentially all citrobacteria (70/71) were found to elaborate enterobactin-like siderophores by both biologic and chemical assays, however only c. koseri (C. diversus) was found to produce aerobactin. The concentration of ethylenediamine di(o-hydroxyphenylacetic acid) (EDDA) required to inhibit the growth of individual Citrobacter strains by depleting free iron ranged from 250 micrograms/ml to 100 micrograms/ml. Iron utilization studies of selected citrobacter isolates indicated that hemin and hematin could reverse the effects of iron limitation on growth under iron-stressed conditions (1000 micrograms/ml of EDDA). Two C. koseri strains grown under iron-restricted conditions showed similar changes in their whole cell protein profiles including induction of high molecular mass proteins (72-83 kDa) which may play a role in iron acquisition under iron-stressed conditions. The collective results support an additional virulence-associated mechanism for C. koseri strains which may help explain the greater pathogenic potential this group has for causing serious extraintestinal disease in humans.

Bacterial Proteins↗
PubMed1973

Fatty acid activation by a lipophilic bacterium.

Cell-free extracts of Nocardia asteroides activated saturated fatty acids from octanoate to octadecanoate, plus docosanoate; maximal activation occurred with dodecanoate. No activation of short-chain fatty acids was observed. The activating enzyme, characterized as an acyl-coenzyme A (Co A) synthetase (acid: Co A ligase [adenosine monophosphate]; EC 6.2.1.3), was localized in the cytoplasm of the cells and had absolute requirements for Co A, adenosine 5'-triphosphate, and Mg(2+). Kinetic data suggested that N. asteroides possessed at least two synthetases: one specific for short-chain fatty acids, and the other specific for medium- and long-chain fatty acids.

Adenosine Monophosphate↗
PubMed2003

Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways.

BACKGROUND AND AIMS: Short chain fatty acids (SCFA) exert profound effects on the colonic mucosa. In particular, SCFA modulate mucosal immune functions. The antimicrobial cathelicidin LL-37 is expressed by colon epithelial cells. In the present study the effect of SCFA on LL-37 expression was investigated. METHODS: LL-37 expression in vivo was assessed by immunohistochemistry. Real time quantitative reverse transcription-polymerase chain reaction was employed to determine LL-37 expression in colonocytes in vitro after treatment with various cytokines, SCFA, or flavone. LL-37 levels were correlated to cell differentiation which was determined by alkaline phosphatase (AP) activity. In addition, intracellular signalling pathways such as MEK-ERK (mitogen/extracellular signal protein kinase (MEK)/extracellular signal regulated protein kinase (ERK)) and p38/mitogen activated protein (MAP) kinase were explored. RESULTS: In vivo, LL-37 expression in healthy mucosa was restricted to differentiated epithelial cells in human colon and ileum. In colonocytes, increased LL-37 expression associated with cell differentiation was detected in vitro following treatment with butyrate, isobutyrate, propionate, and trichostatin A. Flavone induced LL-37 transcription but did not affect AP activity while cytokines had no effect. To dissect pathways mediating differentiation and LL-37 expression, specific inhibitors were applied. Inhibition of the protein kinase MEK enhanced butyrate induced AP activity while LL-37 expression in colon epithelial cells was blocked. In contrast, inhibition of p38/MAP kinase blocked cell differentiation without inhibiting LL-37 expression. CONCLUSIONS: Expression of the cathelicidin LL-37 in colonocytes and cellular differentiation are separately modulated by SCFA via distinct signalling pathways. These data may provide a rationale for dietary modulation of mucosal defence mechanisms.

Adult↗