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)

Several unique proteins accumulate in soybean (Glycine max) leaves when the developing fruits are removed. In the present study, elevated levels of nucleotide pyrophosphatase and phosphodiesterase I activities were present in leaves of defruited soybean plants. The soluble enzyme catalyzing these reactions was purified nearly 1000-fold, producing a preparation that contained a single 72-kD polypeptide. The molecular mass of the holoenzyme was approximately 560 kD, indicating that the native enzyme was likely octameric. The purified enzyme hydrolyzed nucleotide-sugars, nucleotide di- and triphosphates, thymidine monophosphate p-nitrophenol, and inorganic pyrophosphate but not nucleotide monophosphates, sugar mono- and bisphosphates, or NADH. The subunit and holoenzyme molecular masses and the preference for substrates distinguish the soybean leaf nucleotide pyrophosphatase/phosphodiesterase I from other plant nucleotide pyrophosphatase/phosphodiesterase I enzymes. Also, the N-terminal sequence of the soybean leaf enzyme exhibited no similarity to the mammalian nucleotide pyrophosphatase/phosphodiesterase I, soybean vegetative storage proteins, or other entries in the data bank. Thus, the soybean leaf nucleotide pyrophosphatase/phosphodiesterase I appears to be a heretofore undescribed protein that is physically and enzymatically distinct from nucleotide pyrophosphatase/phosphodiesterase I from other sources, as well as from other phosphohydrolytic enzymes that accumulate in soybean leaves in response to fruit removal.
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PMID:Purification and Properties of a Unique Nucleotide Pyrophosphatase/Phosphodiesterase I That Accumulates in Soybean Leaves in Response to Fruit Removal. 1222 43

Insulin resistance is associated with vascular disease. Physiological concentrations of insulin inhibit cultured vascular smooth muscle cell (VSMC) contraction and migration by increasing nitric oxide (NO)-stimulated cGMP accumulation. The failure to do so in insulin-resistant states may aggravate vascular disease. We sought to determine the mechanism of insulin's increase in cGMP accumulation. Isobutylmethylxanthine, an inhibitor of phosphodiesterase activity, inhibited the decline in cGMP levels measured by immunoassay in cGMP-loaded cultured rat aortic VSMCs, but 1 nmol insulin did not. Thus, insulin's increase in cGMP accumulation is due to stimulated production, not inhibited hydrolysis and/or efflux. Insulin, which increases the NADH/NAD+ ratio in these cells, stimulated superoxide anion (O2-) accumulation measured by lucigenin luminescence to 256+/-25% (P<0.05) by a process that was blocked by the NADH oxidase inhibitor diphenyliodonium (DPI) and enhanced by the superoxide dismutase inhibitor diethyldithiocarbonate (DETCA). Insulin also stimulated hydrogen peroxide (H2O2) accumulation measured by horseradish peroxidase/luminol luminescence to 221+/-22% (P<0.05) by a DETCA-sensitive mechanism. H2O2 (100 micromol/L) in the absence of insulin increased NO-stimulated cGMP accumulation to 151+/-11% (P<0.05). Insulin alone increased NO-stimulated cGMP accumulation to 183+/-17% (P<0.05), and this was blocked by either DPI or DETCA. We conclude that insulin increases NADH oxidase-derived O2- production in cultured rat VSMCs. This did not cause the expected scavenging of NO resulting in the reduction of NO-stimulated guanylate cyclase activity, but enough O2- was metabolized to H2O2 to increase overall NO-stimulated cGMP production.
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PMID:Insulin-stimulated hydrogen peroxide increases guanylate cyclase activity in vascular smooth muscle. 1296 80

This study investigated the vasorelaxant activity, superoxide radicals (O2(*-))-scavenging capacity and cyclic nucleotide phosphodiesterase (PDE)-inhibitory effects of hesperidin and hesperetin, two flavonoids mainly isolated from citrus fruits. Hesperetin concentration-dependently relaxed the isometric contractions induced by noradrenaline (NA, 1 microM) or by a high extracellular KCl concentration (60 mM) in intact rat isolated thoracic aorta rings. However, hesperetin (10 microM-0.3 mM) did not affect the contractile response induced by okadaic acid (OA, 1 microM). Mechanical removal of endothelium and/or pretreatment of aorta rings with glibenclamide (GB, 10 microM), tetraethylammonium (TEA, 2 mM) or nifedipine (0.1 microM) did not significantly modify the vasorelaxant effects of this flavonoid. Hesperetin (10 microM-0.1 mM) did not affect the basal uptake of (45)Ca(2+) but decreased the influx of (45)Ca(2+) induced by NA and KCl in endothelium-containing and endothelium-denuded rat aorta. Hesperetin (10 microM-0.1 mM) did not scavenge O2(*-) generated by the phenazine methosulfate (PMS)-reduced beta-nicotinamide adenine dinucleotide (NADH) system. Hesperetin (0.1 mM) significantly reversed the inhibitory effects of NA (1 microM) and high KCl (60 mM) on cyclic nucleotide (cAMP and cGMP) production in cultured rat aortic myocytes. Hesperetin preferentially inhibited calmodulin (CaM)-activated PDE1 and PDE4 isolated from bovine aorta with IC(50) values of about 74 microM and 70 microM respectively. In contrast, the 7-rhamnoglucoside of hesperetin, hesperidin (10 microM-0.1 mM), was inactive in practically all experiments, although it inhibited basal and cGMP-activated PDE2 isolated from platelets (IC(50) values of 32+/-4 microM and 137+/-34 microM respectively). These results suggest that the vasorelaxant effects of hesperetin are basically due to the inhibition of PDE1 and PDE4 activities.
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PMID:Comparative study of the vasorelaxant activity, superoxide-scavenging ability and cyclic nucleotide phosphodiesterase-inhibitory effects of hesperetin and hesperidin. 1559 7

Phenothiazines have been reported for anti-mycobacterial activity by inhibiting calcium binding proteins, potassium transport processes of phagolysosomes, NADH dependent oxygen consumption by M. tuberculosis membranes and DNA, and lipid synthesis of the bacterium. Thioridazine (TZ), chloropromazine (CPZ) and trifluoperazine (TFP) belong to the class of phenothiazines widely used as neuroleptic drugs. Trifluoperazine, a calmodulin antagonist in eukaryotes, binds to a similar protein containing prototypical EF hand to bind to calcium in M. tuberculosis. Calmodulin, a calcium binding protein, plays a critical role in regulating the activities of several enzymes in response to intracellular calcium levels. Since calmodulins are best characterized in eukaryotes as opposed to prokaryotes, the presence of calmodulin-like activity in M. tuberculosis, the causative agent of tuberculosis, is unknown. We have provided biochemical evidence that M. tuberculosis recombinant (r) Rv1211 gene product stimulates the activities of heterologous calcium-deficient NAD-kinase and bovine brain phosphodiesterase (PDE), much like the eukaryotic calmodulins. Further we have shown that EGTA, a calcium chelator, inhibits rRv1211-stimulated NAD-kinase and PDE activities. We have also shown that trifluoperazine interferes with the activation of NAD-kinase and PDE activities by Rv1211. Using a bioinformatics approach, we have shown that Rv1211 contains one prototypical calcium-binding EF-hand motif, a characteristic feature of calmodulins. Based on these data, we conclude that Rv1211 encodes a protein with calmodulin-like activity (CAMLP) in the human pathogen M. tuberculosis and acts as a potential target for trifluoperazine.
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PMID:A novel calcium binding protein in Mycobacterium tuberculosis--potential target for trifluoperazine. 1963 1

The acyl carrier protein (ACP) phosphodiesterase gene (SO 4396) of Shewanella oneidensis MR-1 which was analyzed to have azoreductase activity was heterologously expressed in Escherichia coli. The ACP phosphodiesterase was found to reach maximum enzyme velocity 220.59 U/mg, named azoreductase in this study. The azoreductase had highest specific activity (153.16 U/mg) at pH 6.5, which showed a preference for nicotinamide adenine dinucleotide (NADH) as electron donor. The phylogenetic tree analysis indicated that the azoreductase had preference for NADH and dependence for flavin mononucleotide (FMN). However, the azoreductase from S. oneidensis MR-1 still had high enzyme activity in the absence of FMN. The Mg(2+) had a positive influence on the enzyme activity with 25 mM concentration, whereas Cr(3+), Cd(2+) usually had significantly negative effect on enzyme activity. The purified azoreductase retained nearly 100 % activity after incubating in 30 % dimethyl sulfoxide (DMSO), 30 % acetone, 30 % methanol, 20 % ethanol, 20 % isopropanol, and 10 % propanol.
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PMID:Characterization of an efficient catalytic and organic solvent-tolerant azoreductase toward methyl red from Shewanella oneidensis MR-1. 2308 53


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