Phosphodiesterase-II

The enzyme has also been called spleen phosphodiesterase (1,2) and phosphodiesterase II (3). We prefer to use the term phosphodiesterase as a general name for the broad group of enzymes hydrolyzing phos-phodiester bonds whether between nucleosides or not (4). Table I gives a few examples of such enzymes. The term phosphodiesterase II (3), intended to mean an enzyme releasing nucleoside-3 -phosphates, seems to be an unhappy one, like that of deoxyribonuclease II (5) from... 

Phosphodiesterase II Bovine spleen RNA and DNA (single-stranded) exonudease splits d linkages at 5 end, releasing 3 -phosphonudeosides... 

Primer Removal 1 pi of a 0.5 M acetic add solution was added to the processed primer extension reaction resulting in a reaction pH < 7. Then 2 pi of phosphodiesterase II that was previously dialysed against ammonium citrate (0.1 M, pH 6.0) were added and the reaction was incubated for 1 h at 37°C. 

Golgi cells in the granule cell layer are interneurones involved in modulating input to the Purkinje cells from the mossy fibre pathway. They express phosphodiesterase II (Juilfs etal. 1999). In relation to the number of cells in the cerebellum these represent a minor cell population, however, signal intensity is high suggesting that there is a significant level of phosphodiesterase II protein expressed in these cells. 

Hosono, K., and H. Suzuki Acylpeptides, the Inhibitors of Cyclic Adenosine-3, 5 -monophosphate Phosphodiesterase. II. Amino Acid Sequence and Location of Lactone Linkage. J. Antibiotics 36, 674 (1983). 

In reaction II, the GIcNAc is removed by the action of a phosphodiesterase, leaving the Man residues phos-phorylated in the 6 position ... 

Hashimoto,Y., Sharma, R. K. and Soderling, T. R. Regulation of Ca+2/calmodulin-dependent cyclic nucleotide phosphodiesterase by the autophosphorylated form Ca+2/ calmodulin-dependent protein kinase II. J. Biol. Chem. 264 10884-10887,1989. 

Drugs that affect all phosphodiesterase type 5 inhibitors include the following alcohol, amlodipine, angiotensin II receptor blockers, antacids, bendroflumethiazide, beta blockers, cimetidine, diuretics, enalaphl, metoprolol, nifedipine, rifampin, tacrolimus. 

PEE-IV Inhibitors Selective inhibitors of phosphodiesterase IV (PDE4) are in development for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Two of them contain fluorine atoms roflumilast (preregistered) bears a difluoromethyl ether and AWD-12-281 (Phase II) has a single fluorine atom (Figure 8.51). 

Fig. 5.19. GTP and GDP structures of transducin. The Ga,t subunit of transducin possesses—in contrast to Ras protein and to other small regulatory GTPases —an a-hehcal domain that hides and closes the G-nucleotide binding pocket. The conformational changes that accompany the transition from the inactive G t GDP form (a) into the active G t GTP form (b), are restricted to three structural sections that are known as switches I, II and III. Switch I includes the link of the a-helical domain with P2, switch II affects in particular hehx a2, and switch III, the pS—a3 loop. Switch III includes a sequence that is characteristic for the a-subunits of the heterotrimeric G-proteins. The conformational changes of switches II and III affect structural sections that are assumed to be binding sites for the effector molecule adenylyl cyclase (AC) and the y-subunit of cGMP-dependent phosphodiesterase (PDEy), based on mutation experiments and biochemical investigations. MOLSKRIPT representation according to Krauhs, (1991).

The conclusion of Bernardi and Griffe (3) that the phosphodiesterase activity of acid DNase is an intrinsic property of the enzyme molecule has been recently challenged by Slor (46, 58), Swenson and Hodes (54), and Slor and Hodes (55), who claimed to have obtained a separation of the two activities. In fact, none of the reported results proves an actual separation of the two activities and constitutes an acceptable evidence against the two activities being carried by the same protein molecule. Some data suggest, however, that the phosphodiesterase activity may be inactivated preferentially by some treatments. In connection with the phosphodiesterase activity of acid DNase, see also Tables I and II in reference (56) and the related discussion (56a). 

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