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)

Inzolen, a combination of the potassium, magnesium, copper, manganese and cobalt salts of aspartic acid, inhibits the second phase of ADP-induced aggregation probably by affecting the membrane-located adenylatecyclase/phosphodiesterase system. Correspondingly inzolen affects the activation of platelet factor 3 (PF3), which is also located in the platelet membrane. Thus spontaneous as well as kaolin-induced platelet factor availability is reduced by inzolen. The significant inhibition of factor 3 availability can be interpreted by a magnesium-mediated activation of phosphoryltransferases.
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PMID:[Potassium, magnesium, copper, manganese and cobalt salts of aspartic acid on platelet factor 3 availability (author's transl)]. 719 69

Of 13 Rhizobium and Bradyrhizobium strains investigated for the production of cellular and extracellular phosphodiesterase and phosphotriesterase, all were found to produce both enzymes. Phosphodiesterase was produced at a much higher level than phosphotriesterase. Rhizobium meliloti TAL 1373 was the most productive. The extracellular enzymes were activated by inclusion in the assay mixture of Ca2+ or Mg2+. The enzymes were inhibited by Zn2+ but not significantly affected by Cu2+, Co2+ and Mn2+. Both hydrolases were inhibited by dithiothreitol but not by thiol-directed inhibitors, suggesting that sulphydryl groups are not directly involved in catalysis. The enzymes have the ability to hydrolyse some organophosphorus compounds, suggesting that Rhizobium and Bradyrhizobium strains play an important role in the degradation of organophosphorus pesticides.
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PMID:Phosphodiesterase and phosphotriesterase in Rhizobium and Bradyrhizobium strains and their roles in the degradation of organophosphorus pesticides. 776 98

cGMP-binding cGMP-specific phosphodiesterase (cG-BPDE) binds tightly to a Zn(2+)-chelate column (Francis, S. H., and Corbin, J. D. (1988) Methods Enzymol. 159, 722-729). Using three different approaches, Zn2+ is now shown to bind to cG-BPDE, and the Kd is determined to be approximately 0.5 microM, with a binding stoichiometry of approximately 3 mol of Zn2+/mol of monomer. A similar concentration range of Zn2+ (0.05-1 microM Zn2+) also supports phosphodiesterase (PDE) catalytic activity. The Zn2+ binding to cG-BPDE is not diminished by, nor is catalysis supported by, relatively high concentrations of Cu2+, Cd2+, Ca2+, or Fe2+. Neither cGMP nor 3-isobutyl-1-methylxanthine affects Zn2+ binding under the conditions used. Mn2+, Co2+, or Mg2+ supports catalysis, but only at significantly higher concentrations (4-, 15-, and 250-fold, respectively) than that required for Zn2+. Two tandem amino acid sequences, which are conserved in the catalytic domains of all characterized mammalian PDEs, resemble the single sequence motif that has been shown to coordinate Zn2+ in the catalytic sites of Zn2+ hydrolases such as thermolysin.
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PMID:Zinc interactions and conserved motifs of the cGMP-binding cGMP-specific phosphodiesterase suggest that it is a zinc hydrolase. 807 92

This paper describes the purification and properties of a 2',3'-cyclic nucleotide 3'-phosphodiesterase which hydrolyzes nucleoside 2',3'-cyclic monophosphates to nucleoside 2'-phosphates. The enzyme is present in encysted gastrulae of Artemia and its specific activity greatly increases during larval development. The purified enzyme has a molecular weight of around 55 000 as estimated by gel filtration, does not require metals for activity, is inhibited by Zn2+ and inactivated by Cu2+ and has a pH optimum at around neutrality. Based on the relative values of V(max)/Km, the specificity of the phosphodiesterase toward the four 2',3'-cyclic nucleotides is Guo-2',3'-P > Ado-2',3'-P > Cyd-2',3'-P > Urd-2',3'-P = 45:36:20:7. The enzyme from Artemia gastrulae is competitively inhibited by the four nucleosides 2'-phosphates (Ki values around 1 mM) while the enzyme from larvae is only inhibited by the purine nucleotides. The phosphodiesterase characterized in this work is more similar in substrate specificity to the 2',3'-cyclic nucleotide 3'-phosphodiesterase from the mammalian nervous system than to the plant enzyme. The functional relationship of this enzyme with the Artemia ribonuclease VI is discussed.
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PMID:Purification and characterization of Artemia 2',3'-cyclic nucleotide 3'-phosphodiesterase. 864 16

A Zn(2+)-glycerophosphocholine cholinephosphodiesterase was purified with a specific activity of 4.6 mumole/min.mg protein from bovine brain membranes by procedures involving PI-PLC solubilization, concanavalin A affinity chromatography, CM-sephadex chromatography and Sephadex G-150 chromatography. Based on molecular weight determination gel chromatography and SDS polyacrylamide gel electrophoresis, the phosphodiesterase activity appears to be a dimeric protein (110 kDa) composed of two subunits with a molecular weight of approximately 54 kDa. The K(m) value for p-nitrophenylphosphocholine and the optimum pH were found to be 16 microM and pH 10.5, respectively. The phosphodiesterase was inhibited by Cu2+, but not the other divalent metal ions. The activity of the apoenzyme was remarkably activated by Co2+ or Zn2+, but not Mn2+ or Mg2+. In addition, the inactivation of the enzyme in glycine buffer was prevented by Mn2+ or Zn2+, but not Co2+ or Mg2. In a separate experiment, comparing properties of the purified and membrane-bound phosphodiesterases, the forms of two enzymes were quite similar except in stability. Both enzymes were more stable at pH 7.4 than pH 5 or 10. However, the membrane-bound enzyme was more stable than the soluble enzyme at all three pHs. These data suggest that the activity of the phosphodiesterase may be stabilized in-vivo.
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PMID:Properties of a Zn(2+)-glycerophosphocholine cholinephosphodiesterase from bovine brain membranes. 892 80

In the current study, Cu2+ was tested for its ability to relax vessels and to accumulate cyclic GMP (cGMP) in rat pulmonary artery employing rat extrapulmonary arterial rings. Cu(2+)-induced relaxation was endothelium and concentration (in the range from 10(-7) to 10(-4) M) dependent. The content of cGMP in the rings was increased 1.7-fold with 10(-4) M Cu2+. NG-Monomethyl-L-arginine abolished both the copper-induced relaxation and the increase in cGMP of rings. Cu2+ and zaprinast, which inhibits phosphodiesterase activity, caused a synergistic increase in cGMP level in the rings, suggesting that Cu2+ enhanced cGMP level through a mechanism different from that of zaprinast, probably as a consequence of elevated accumulation of nitric oxide (NO). The magnitude of vasorelaxation observed due to simultaneous addition of Cu2+ and acetylcholine was additive, not synergistic. Cu2+ did not augment relaxation induced by exogenously added NO donor. These results suggest that Cu2+ elevates NO level in the rings not by prolonging the half-life of NO, but by activation of endothelial nitric oxide synthase and subsequently potentiating the action of NO on vascular tone.
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PMID:The effect of Cu2+ on rat pulmonary arterial rings. 903 Aug 97

The effect of divalent metal ions on the activity of glycerophosphocholine cholinephosphodiesterse from ox brain was examined. Zn(2+)- and Co(2+)-glycerophosphocholine cholinephosphodiesterases were prepared from the exposure of apoenzyme to Zn2+ and Co2+, respectively, and the properties of two metallo-phosphodiesterases were compared to those of native phosphodiesterase. Although two metallo-enzymes were similar in expressing Km value, optimum pH or sensitivity to Cu2+, they differed in the susceptibility to the inhibition by thiocholine or tellurite; while Co(2+)-phosphodiesterase was more sensitive to tellurites, Zn(2+)-phosphodiesterase was more susceptible to inhibition by thiocholine. In addition, Zn(2+)-phosphodiesterase was more thermo-stable than Co2+ enzyme. Separately, when properties of native phosphodiesterase were compared to those of each metallo-phosphodiesterase, native phosphodiesterase was found to be quite similar to Zn(2+)-phosphodiesterase in many respects. Even in thermo-stability, native enzyme resembled Zn(2+)-phosphodiesterase rather than Co(2+)-enzyme. Consistent with this, the stability of native phosphodiesterase was maintained in the presence of Zn2+, but not Co2+, Mn2+ was also as effective as Zn2+ in the stabilization of the enzyme. Noteworthy, the native enzyme was found to be inhibited competitively by Cu2+ with a Ki value of 20 microM, and its inhibitory action was antagonized effectively by Zn2+ or Co2+. Also, choline, another competitive inhibitor of the enzyme, appeared to antagonize the inhibitory action of Cu2+. Taken together, it is suggested that there may be multiple binding sites for divalent metal ions in the molecule of glycerophosphocholine cholinephosphodiesterase.
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PMID:Interaction of divalent metal ions with Zn(2+)-glycerophosphocholine cholinephosphodiesterase from ox brain. 935 12

Zn2+-glycerophosphocholine cholinephosphodiesterase, responsible for the conversion of glycerophosphocholine into glycerol and phosphocholine, was inactivated during incubation with ascorbic acid at 38 degrees C. The inclusion of copper ions or Fe2+ accelerated the ascorbate-induced inactivation, with Cu2+ or Cu+ being much more effective than Fe2+, suggestive of ascorbate-mediated oxidation. Dehydroascorbic acid had no effect on the phosphodiesterase, but H2O2 inactivated the enzyme in a concentration-dependent manner. Also, the enzyme was inactivated partially by a superoxide anion-generating system but not an HOCl generator. In support of involvement of H2O2 in the ascorbate action, catalase and superoxide dismutase expressed a complete and a partial protection, respectively. However, hydroxy radical scavengers such as mannitol, benzoate, or dimethyl sulfoxide were incapable of preventing the ascorbate action, excluding the participation of extraneous .OH. Although p-nitrophenylphosphocholine exhibited a modest protection against the ascorbate action, a remarkable protection was expressed by amino acids, especially by histidine. In addition, imidazole, an electron donor, showed a partial protection. Separately, when Cu2+-induced inactivation of the phosphodiesterase was compared with the ascorbate-mediated one, the protection and pH studies indicate that the mechanism for the ascorbate action is different from that for the Cu2+ action. Here, it is proposed that Zn2+-glycerophosphocholine cholinephosphodiesterase is one of brain membrane proteins susceptible to oxidative inactivation.
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PMID:Ascorbate-induced oxidative inactivation of Zn2+-glycerophosphocholine cholinephosphodiesterase. 948 38

The cAMP antagonist, prostaglandylinositol cyclic phosphate (cyclic PIP), is synthesized from prostaglandin E and activated inositol phosphate. From various tissues only that amount of cyclic PIP can be isolated that constitutes the difference between synthesis and degradation. In order to overcome this drawback, the cyclic PIP degrading enzyme or enzymes had to be characterized prior to searching for inhibitors. Cyclic PIP degrading activities have been found in all rat tissues tested, and are lowest in brain (380 pmol x min(-1) x g(-1) wet weight) and highest in liver (1460 pmol x min(-1) x g(-1) wet weight). They are associated primarily with particulate structures of the cells, but not with the plasma membrane. There appear to be at least two different enzymatic activities involved in the degradation of cyclic PIP, because there are two pH-optima, one between pH 7 and 8 and another between pH 4 and 5. It is assumed that these activities are located in microsomes and lysosomes. Because prostaglandylinositol is the final product obtained in the degradation of cyclic PIP, a phosphodiesterase and a phosphatase should be involved, which could not yet be identified individually. Like alkaline phosphatase, cyclic PIP-degrading enzymes require Mg2+ and they are inhibited by heavy metal ions such as mercuric and copper chloride, by sodium fluoride and interestingly, by prostaglandins.
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PMID:Degradation of the cyclic AMP antagonist prostaglandylinositol cyclic phosphate (cyclic PIP) by dephosphorylation. 1006 41

A phosphodiesterase was purified from the venom of the snake Bothrops alternatus by a combination of gel filtration and ion exchange chromatographies. In SDS-PAGE, the enzyme gave a single band with a molecular mass of 105 kDa, which was unaltered in the presence of beta-mercaptoethanol, indicating that the protein contained no subunits. A single protein band was also observed in native PAGE. There were no contaminating 5'-nucleotidase, alkaline phosphatase and protease activities. The enzyme was recognized by commercial bothropic antiserum and gave a single band in immunoblotting. The enzyme had a pH optimum in the range of 7.5-9.5 and the optimum temperature was 60 degrees C, with activity being rapidly lost within 1 min at > or = 70 degrees C. The Km of the enzyme was 2.69 mM. PDE activity was potentiated by cobalt and, to a lesser extent, by calcium, whereas copper, manganese, zinc, EDTA, and beta-mercaptoethanol were inhibitory. These properties show that this enzyme is very similar to that isolated from other snake venoms.
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PMID:Purification and characterization of a phosphodiesterase from Bothrops alternatus snake venom. 1263 51


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