Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The promoter-proximal gene (glpT) of the glpT-glpQ operon of Escherichia coli encodes a membrane permease responsible for active transport of sn-glycerol 3-phosphate. Promoter-distal glpQ encodes a periplasmic protein which is not required for active transport of sn-glycerol 3-phosphate (Larson, T.J., Schumacher, G., and Boos, W. (1982) J. Bacteriol. 152, 1008-1021). This periplasmic protein has now been identified as a phosphodiesterase which hydrolyzes glycerophosphodiesters into sn-glycerol 3-phosphate plus alcohol. The enzyme exhibited broad substrate specificity with respect to the alcohol moiety; sn-glycerol 3-phosphate was released from glycerophosphoethanolamine, glycerophosphocholine, glycerophosphoglycerol, and bis(glycerophospho)glycerol. The enzyme was specific for glycerophosphodiesters; bis(p-nitrophenyl)phosphate, a substrate for other phosphodiesterases, was not hydrolyzed. In a coupled spectrophotometric assay utilizing sn-glycerol 3-phosphate dehydrogenase and NAD, apparent activity was optimal at pH 9 and was stimulated by Ca2+. The substrates of the phosphodiesterase had no affinity for the glpT-encoded active transport system. Thus, the glpQ gene product expands the catabolic capability of the glp regulon to include a variety of glycerophosphodiesters.
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PMID:Periplasmic glycerophosphodiester phosphodiesterase of Escherichia coli, a new enzyme of the glp regulon. 630 89

Nuclei isolated from rat liver were incubated with NAD whose two ribose moieties were respectively labeled with 3H or 14C. By enzymatic (phosphodiesterase) and/or chemical (hydroxylamine) attack on doubly labeled ADP-ribosylated nuclear residues, AMP was found after hydroxylaminolysis as well as iso-ADP-ribose after phosphodiesterase plus hydroxylamine, in the absence of detectable amounts of ribose-5-phosphate. This is taken to indicate the existence of additional ribose-protein binding sites in in vitro ADP-ribosylated nuclear proteins: Besides C-1" (Hayaishi et al., Stocken et al.) C-2' and/or C-3' (purine-near) as well as C-2" and/or C-3" (pyrimidine-near), not only at the end but also within the chain of oligo-ADPR.
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PMID:A note on the ADP-ribose-protein linkages in rat-liver nuclei: a possible approach to assessing megavitamin therapy with niacin. 630 20

The membrane-bound enzyme responsible for the breakdown of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) has been purified 1,900-fold from detergent-solubilized human placenta, using chromatographies on Con A-Sepharose, Blue Sepharose, AMP-Agarose, and Sepharose CL-6B, and sucrose density gradient centrifugation. The enzyme required Mg2+ and showed the optimum activity at pH 9.4. The preparation was free of alkaline phosphatase [EC 3.1.3.1], phosphodiesterase [EC 3.1.4.1], and 5'-nucleotidase [EC 3.1.3.5] activities, which enabled investigation of the substrate specificity and kinetic properties of the enzyme without interference by secondary reactions due to the above activities. The enzyme cleaved the pyrophosphate linkages of NAD and various sugar nucleotides and the phosphodiester linkage of p-nitrophenyl-thymidine 5'-monophosphate (PNTP), as well as the phosphosulfate linkages of PAPS and its biosynthetic precursor, adenosine 5'-phosphosulfate (APS), with apparent Km values of 0.12-0.33 mM. Relative activities towards PNTP and PAPS did not change during the purification procedures starting from the homogenate. This, together with the data of kinetic studies using two substrates simultaneously, led us to conclude that the activities towards all the substrates tested were due to one and the same nucleotide pyrophosphatase.
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PMID:Substrate specificity of a nucleotide pyrophosphatase responsible for the breakdown of 3'-phosphoadenosine 5'-phosphosulfate (PAPS) from human placenta. 630 61

Three distinct enzymes hydrolyzing either ApppA or AppppA, or both, were separated and purified from yellow lupin seed extracts. Two of the enzymes were purified to homogeneity. These enzymes differ greatly in their catalytic and physical properties. One hydrolase, with a native molecular weight of 41,000, exhibits broad pH (from 5-8) optimum for activity, requires Mg2+ for activity, is inhibited by zinc ions (I0.5 = 25 microM) and hydrolyses ApppA (V = 1), ApppC (V = 0.38), ApppG (V = 0.2), and ribose(5')pppA (V = 0.2). The enzyme exhibits much lower activity with AppppA (V = 0.1), and ApppppA, AppppppA, ppppA, and ATP are hydrolyzed 25- to 100-fold slower then ApppA. ADP was always one of the products of the reactions catalyzed by the enzyme. AppA, NAD, NADP, FAD, cAMP, and p-nitrophenyl-thymidine 5'-phosphate were not hydrolyzed by the enzyme. The enzyme is diadenosine 5',5"'-P1, P3-triphosphatase. The second hydrolase, composed of one polypeptide chain of a molecular weight 18,000-18,500, exhibits optimal activity in the pH range from 7.5-9, requires Mg2+ for activity, is inhibited by calcium ions (I0.5 for calcium depends on the concentration of Mg2+ and is 35-180 microM in the presence of 0.5-10 mM Mg2+, respectively), and hydrolyzes AppppA (V = 1, Km = 1 microM), ApppppA (V = 0.42, Km = 1.8 microM), AppppppA (V = 0.34), AppppU (V = 0.73), AppppC (V = 0.67), AppppG (V = 0.27), and ppppA. ATP was always one of the products of the reactions catalyzed by the enzyme. Dinucleoside di- and triphosphates, ATP, cAMP, and p-nitrophenylthymidine 5'-phosphate were not hydrolyzed by the enzyme. This enzyme is diadenosine 5',5"'-P1,P4-tetraphosphatase (EC 3.6.1.17). The third hydrolase, composed of one polypeptide chain of a molecular weight of 56,000, exhibits maximal activity at pH 9-10.5, does not require Mg2+ ions for activity, is inhibited neither by divalent cations (Mg2+, Ca2+, Zn2+, Co2+, Mn2+, or Ni2+) nor by EDTA, and uses as substrates all compounds which are substrates for the diadenosine 5',5"'-P1,P3-triphosphatase and diadenosine 5',5"'-P1,P4-tetraphosphatase. In addition, the enzyme hydrolyzes p-nitrophenyl-thymidine 5'-phosphate, p-nitrophenylthymidine 3'-phosphate, bis-p-nitrophenylphosphate, ADP, AppA, NAD, NADP, and FAD, but not cAMP. With the exception of p-nitrophenylphosphate derivatives all other substrates of the enzyme yield AMP as one of the products of hydrolysis. This enzyme has a specificity similar to that of phosphodiesterases (EC 3.1.4.1) from other sources. With the lupin phosphodiesterase, ApppA (V = 1, Km = 2.2 microM) and AppppA (V = 1, Km = 2.0 microM) are better substrates than NAD (V = 0.8, Km = 9.6 microM), AppA (V = 0.4), ApppppA (V = 0.6), and AppppppA (V = 0.34).
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PMID:Enzymes hydrolyzing ApppA and/or AppppA in higher plants. Purification and some properties of diadenosine triphosphatase, diadenosine tetraphosphatase, and phosphodiesterase from yellow lupin (Lupinus luteus) seeds. 630 93

Islet-activating protein catalyzes the ADP-ribosylation of transducin, a guanine nucleotide-binding regulatory protein that mediates activation of a retinal cyclic GMP-selective phosphodiesterase. Radiolabel from [adenylate-32P]NAD+ was incorporated specifically into the alpha subunit of purified transducin. Maximal levels of incorporation approximated 0.8 mol of ADP-ribose/mol of transducin. A peptide containing the ADP-ribosyl moiety was purified from a tryptic digest of radiolabeled transducin. This peptide was characterized by chemical and enzymatic procedures and by fast atom bombardment mass spectrometry. The primary structure of this peptide was Glu-Asn-Leu-Lys-Asn(ADP-ribose)-Gly-Leu-Phe. It is probable that the peptide originated from the carboxyl terminus of the alpha subunit and that the ADP-ribosyl moiety is attached by an N-glycosidic linkage to the asparagine residue. Transducin associated with retinal disc membranes is also ADP-ribosylated by cholera toxin. Cholera toxin and islet-activating protein sequentially catalyze the incorporation of 1.9 mol of ADP-ribose/mol of transducin, indicating two distinct sites of ADP-ribosylation within transducin.
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PMID:ADP-ribosylation of transducin by islet-activation protein. Identification of asparagine as the site of ADP-ribosylation. 658 63

A 60- to 70-fold purification of an NAD+ glycohydrolase from the inner membrane of rat liver mitochondria to apparent homogeneity on sodium dodecyl sulfate (SDS)-polyacrylamide slab gel is described. The minimum molecular weight of the enzyme on polyacrylamide gels in the presence of SDS is around 62,000. The enzyme splits NAD+ to ADP-ribose and, presumably, nicotinamide. No phosphatase or phosphodiesterase activity is detected in the purified enzyme preparation. The enzyme shows high activity with NAD+ and moderate activity with NADP+ as substrates NAD(P)Hs are poor substrates. ATP and nicotinamide inhibit the enzyme. A possible participation of the enzyme in the mechanism of calcium release from rat liver mitochondria is discussed.
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PMID:Purification and properties of a mitochondrial NAD+ glycohydrolase. 687 Feb 60

Tolbutamide, gliclazide and glibenclamide failed to stimulate glucose oxidation in rat pancreatic islets. Tolbutamide also failed to stimulate pyruvate and palmitate oxidation and decreased the islet content of NAD(P)H and ATP. Tolbutamide stimulated 45Ca net uptake, inhibited 86Rb net uptake and tended to increase 22Na net uptake by the islets. The effect of theophylline upon islet function differed from that of tolbutamide by the magnitude of its insulinotropic action as a function of the glucose concentration, by its stimulant action upon the utilization of endogenous nutrients in islets deprived of glucose and by the lack of gross alteration in 45Ca and 86Rb net uptake. It is concluded that the insulinotropic effect of hypoglycemic sulfonylureas cannot be merely equated to a facilitation of nutrient metabolism or inactivation of phosphodiesterase in the islet cells. The primary action of these drugs could be to affect cations transport across the B-cell membrane.
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PMID:Metabolic, cationic and secretory effects of hypoglycemic sulfonylureas in pancreatic islets. 699 64

The major acidic fibroblast growth factor (aFGF)-stimulated phosphoprotein (MAFP) purified from bovine liver exhibits kinase, autoadenylylation, and alkaline nucleotide phosphodiesterase activities depending upon reaction conditions. In the presence of divalent ions, MAFP showed intrinsic and a FGF-stimulated kinase activities (autophosphorylation) using either [gamma-32P]ATP or [gamma-32P]GTP as a substrate. The autophosphorylation activity of MAFP was stimulated at low concentrations of Ca2+, Mg2+, or Mn2+ (0.2-2 microM). Depletion of the divalent ions by EDTA abolished the autophosphorylation activity but enhanced the autoadenylylation activity of MAFP. [alpha-32P]ATP as well as [alpha-32P]NAD could serve as substrates for autoadenylylation activity of MAFP. aFGF appeared to enhance the autoadenylylation activity of MAFP with an optimal concentration (0.6-1.2 nM). P1, P3-di(adenosine-5')-triphosphate (AP3A) was found to be a potent inhibitor for the autophosphorylation and autoadenylylation activities of MAFP. Analyses by automated Edman degradation of the adenylylated and phosphorylated peptides derived from autoadenylylated and autophosphorylated MAFP revealed that both autoadenylylation and autophosphorylation occurred at residue Thr204. The kinase and autoadenylylation activities of MAFP had an optimal pH of 6.9-7.4. However, at pH 8.9, MAFP showed intrinsic and aFGF-stimulated phosphodiesterase activities. aFGF appeared to stimulate the phosphodiesterase activity of MAFP without altering the Km (approximately 0.2 mM) of its substrate.
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PMID:The major acidic fibroblast growth factor (aFGF)-stimulated phosphoprotein from bovine liver plasma membranes has aFGF-stimulated kinase, autoadenylylation, and alkaline nucleotide phosphodiesterase activities. 750 70

Integrin alpha 7 is a major substrate in skeletal muscle cells for the cell surface, glycosylphosphatidylinositol-anchored, arginine-specific ADP-ribosyltransferase. Since ADP-ribosylarginine hydrolase, the enzyme responsible for cleavage of the ADP-ribosylarginine bond and a component with the transferase of a putative ADP-ribosylation cycle, is cytosolic, the processing of ADP-ribosylated integrin alpha 7 was investigated. Following incubation of differentiated mouse C2C12 myoblasts with [adenylate-32P]NAD and analysis by SDS-polyacrylamide gel electrophoresis under reducing conditions, two [32P]ADP-ribosylated forms of integrin alpha 7 were resolved. By pulse-chase and purification of the radiolabeled proteins on a laminin affinity column, it was demonstrated that a 105-kDa ADP-ribosylated form originated from a mono-ADP-ribosylated 102-kDa form and represented integrin alpha 7 modified at more than one site. The additional site(s) of modification, utilized at higher NAD concentrations, were located in the 63-kDa N-terminal segment of integrin alpha 7. Both [32P]ADP-ribosylated integrins were loosely associated with the cytoskeleton, bound to laminin affinity columns, and immunoprecipitated with antibodies to integrin beta 1. 32P label was rapidly removed from [32P]ADP-ribosylated integrin alpha 7 at either site of modification, a process inhibited by free ADP-ribose or p-nitrophenylthymidine-5'-monophosphate, an alternative substrate of 5'-nucleotide phosphodiesterase. The processed integrin alpha 7 was unavailable for subsequent ADP-ribosylation, although the amount of surface integrin alpha 7 remained constant. During the processing, no loss of label was observed from integrin alpha 7 radiolabeled with [14C]NAD, containing 14C in the nicotinamide proximal ribose, consistent with degradation of the ADP-ribose moiety by a cell surface 5'-nucleotide phosphodiesterase. Thus, cell surface ADP-ribosylation, in contrast to intracellular ADP-ribosylation, is not readily reversed by ADP-ribosylarginine hydrolase and seems to operate outside the postulated ADP-ribosylation cycle.
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PMID:Processing of ADP-ribosylated integrin alpha 7 in skeletal muscle myotubes. 772 41

Glutamine synthetase (GS) inactivation was observed in crude cell extracts and in the high-speed supernatant fraction from the cyanobacterium Synechocystis sp. strain PCC 6803 following the addition of ammonium ions, glutamine, or glutamate. Dialysis of the high-speed supernatant resulted in loss of inactivation activity, but this could be restored by the addition of NADH, NADPH, or NADP+ and, to a lesser extent, NAD+, suggesting that inactivation of GS involved ADP-ribosylation. This form of modification was confirmed both by labelling experiments using [32P]NAD+ and by chemical analysis of the hydrolyzed enzyme. Three different forms of GS, exhibiting no activity, biosynthetic activity only, or transferase activity only, could be resolved by chromatography, and the differences in activity were correlated with the extent of the modification. Both biosynthetic and transferase activities were restored to the completely inactive form of GS by treatment with phosphodiesterase.
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PMID:ADP-ribosylation of glutamine synthetase in the cyanobacterium Synechocystis sp. strain PCC 6803. 776 63


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