Phosphodiesterase

Tyrosyl-DNA phosphodiesterase (TDP) cleaves the phosphodiester bond linking the active site tyrosine residue of topoisomerase I with the 3¢ terminus of DNA in topoisomerase I–DNA complexes which accumulate during treatment of cancer with camptothecin. In yeast, TDP mutation confers a 1000-fold hypersensitivity to camptothecin in the presence of an additional mutation of RAD9 gene [Pouliot, J.J., Yao, K.C., Robertson, C.A. & Nash, H.A. (1999) Science 286, 552–555].

8p research12 01-06-2013 34 2   Download

Here, we show that recombinant bovine PDE5A1 is pro-teolysedby recombinant caspase-3 inin vitroand transfected Cos-7 cells. In addition, the treatment of PDE5A1-trans-fectedCos-7andPC12cellswithstaurosporine, anapoptotic agent that activates endogenous caspase-3, also induced proteolysis and inactivation of PDE5A1. These findings suggest that there is specificity in the interaction between caspase-3 and PDE5A1 that requires application of an apoptotic stimulus.

9p tumor12 20-04-2013 57 5   Download

Diadenosine polyphosphates (ApnAs) act as extracellular signaling molecules in a broad variety of tissues. They were shown to be hydrolyzed by surface-located enzymes in an asymmetric manner, generating AMP and Apn-1 from ApnA. The molecular identity of the enzymes responsible remains unclear.We analyzed the potential ofNPP1, NPP2, and NPP3, the three members of the ecto-nucleotide pyro-phosphatase/phosphodiesterase family, to hydrolyze the diadenosine polyphosphates diadenosine 5¢,5¢¢¢-P 1 ,P 3 -triphosphate (Ap3A),...

8p fptmusic 16-04-2013 32 2   Download

On the basis of amino acid sequences and crystal structures of similar enzymes, it is proposed that Met95 of the heme-regulatedphosphodiesterase fromEscherichiacoli(EcDOS) acts as aheme axial ligand. Inaccordancewith this proposal, the Soret and visible optical absorption and magnetic circular dichroism spectra of the Fe(II) complexes of the Met95Ala and Met95Leu mutant proteins indicate that these complexes are five-coordinated high-spin, suggesting that Met95 is an axial ligand for the Fe(II) complex. ...

9p fptmusic 12-04-2013 38 3   Download

In haem-regulated phosphodiesterase (PDE) fromEscheri-chia coli(EcDOS), haem is bound to the PAS domain, and the redox state of the haem iron regulates catalysis by the PDEdomain.We generatedmutants ofAsp40, which forms a hydrogen bondwithHis77 (a proximal haemaxial ligand) via twowater molecules, and a salt bridge withArg85 at the protein surface. The redox potential of haem was markedly increased from67 mVvs. the standardhydrogenelectrode in the wild-type enzyme to 95 mV and 114 mV in the Ala and Asn mutants, respectively. ...

6p awards 05-04-2013 42 5   Download

Cyclic nucleotide specific phosphodiesterases (PDEs) are important components of all cAMP signalling networks. In humans, 11 different PDE families have been identified to date, all of which belong to the class I PDEs. Pharmaco-logically, theyhavebecome of great interest as targets for the development of drugs for a large variety of clinical condi-tions. PDEs in parasitic protozoa have not yet been exten-sively investigated, despite their potential as antiparasitic drug targets.

11p dell39 03-04-2013 40 4   Download

Cyclic-nucleotide-specific phosphodiesterases (PDEs) are key players in the intracellular signaling pathways of the important human pathogen Trypano-soma cruzi. We report herein the identification of an unusual PDE from this protozoal organism. This enzyme, TcrPDEC, is a member of the class I PDEs, as determined from the presence of a characteristic signature sequence and from the conservation of a number of functionally important amino acid residues within its catalytic domain.

11p dell39 27-03-2013 41 2   Download

The heme-regulated phosphodiesterase fromEscherichia coli(EcDOS), which is a heme redox-dependent enzyme, is active with a ferrous heme but inactive with a ferric heme. Global structural changes including axial ligand switching and a change in the rigidity of the FG loop accompanying the heme redox change may be related to the dependence ofEcDOS activity on the redox state.

14p inspiron33 26-03-2013 30 5   Download

Regeneration-induced CNPase homolog (RICH) is an axonal growth-associated protein, which is induced in teleost fish upon optical nerve injury. RICH consists of a highly acidic N-terminal domain, a catalytic domain with 2¢,3¢-cyclic nucleotide 3¢-phosphodiesterase (CNPase) activity and a C-terminal isoprenylation site.

10p galaxyss3 21-03-2013 33 5   Download

The C-terminal catalytic domains of the 11 mammalian phosphodiesterase families (PDEs) are important drug targets. Five of the 11 PDE families contain less well-characterized N-terminal GAF domains. cGMP is the lig-and for the GAF domains in PDEs 2, 5, 6 and 11, and cAMP is the ligand for PDE10.

10p galaxyss3 21-03-2013 32 3   Download

The tandem GAF domain of human phosphodiesterase 11A4 (hPDE11A4) requires 72lmcGMP for half-maximal effective concentration (EC50)ofa cyanobacterial adenylyl cyclase used as a reporter enzyme. Here we exam-ine whether modifications in the N-terminus of PDE11A4 affect cGMP sig-nalling.

8p media19 06-03-2013 33 2   Download

Different inhibitors of the Ca 2+ ⁄calmodulin-stimulated phosphodiester-ase 1 family have been described and used for the examination of phospho-diesterase 1 in cellular, organ or animal models. However, the inhibitors described differ in potency and selectivity for the different phosphodiester-ase family enzymes, and in part exhibit additional pharmacodynamic actions.

13p media19 04-03-2013 18 1   Download

ACTH-stimulated aldosterone secretion can be inhibited by atrio-natri-uretic peptide⁄cGMP. The mechanism behind this modulation has been reported to involve cGMP-dependent activation of phosphodiesterase 2 (PDE2) and hydrolysis of cAMP. Recently it was reported that activation of cGMP-dependent protein kinase II (cGKII) stimulated aldosterone secretion in rat zona glomerulosa cells.

10p vinaphone15 27-02-2013 32 2   Download

Retinal photoreceptor phosphodiesterase (PDE6), a key enzyme for photo-transduction, consists of a catalytic subunit complex (Pab) and two inhibi-tory subunits (Pcs). Pabhas two noncatalytic cGMP-binding sites. Here, using bovine PDE preparations, we show the role of these cGMP-binding sites in PDE regulation.

19p cosis54 05-01-2013 44 5   Download

Molecular dynamics simulations employing a combined quantum mechani-cal and molecular mechanical potential have been carried out to elucidate the reaction mechanism of the hydrolysis of a cyclic nucleotide cAMP sub-strate by phosphodiesterase 4B (PDE4B).

17p cosis54 05-01-2013 44 4   Download

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành y học dành cho các bạn tham khảo đề tài: Phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension: a case report...

5p thulanh27 14-12-2011 46 3   Download

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Phosphodiesterase 4 inhibition but not beta-adrenergic stimulation suppresses tumor necrosis factor-alpha release in peripheral blood mononuclear cells in septic shock...

9p coxanh_3 27-10-2011 51 2   Download

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Phosphodiesterase 3 inhibition and cough in elderly asthmatics...

6p coxanh_4 26-10-2011 37 2   Download

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Critical Care giúp cho các bạn có thêm kiến thức về ngành y học đề tài: Metabolic effects of phosphodiesterase III inhibitors: another reason to promote their use?

2p coxanh_3 25-10-2011 29 4   Download

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài:" Lung vasodilatory response to inhaled iloprost in experimental pulmonary hypertension: amplification by different type phosphodiesterase inhibitors...

11p toshiba14 22-10-2011 48 5   Download