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Abstract:

Cyclic nucleotide phosphodiesterases (PDEs) catalyze the degradation of cAMP and cGMP, and regulate a variety of cellular processes by controlling the levels of these second messengers. We have previously described the presence of both a calcium-stimulated adenylyl cyclase and two membrane-bound cAMP-specific PDEs (one of them strongly associated to the flagellum and the other one with a possible vesicular localization) in Trypanosoma cruzi. Here we report the identification and characterization of TcrPDEA1, a singular phosphodiesterase of T. cruzi which is resistant to the typical phosphodiesterase inhibitors, such as IBMX, papaverine and theofylline. TcrPDEA1 is a single copy gene that encodes a 620-amino acid protein, which is grouped with PDE1 family members, mainly with its kinetoplastid orthologs. TcrPDEA1 was able to complement a mutant yeast strain deficient in PDE genes, demonstrating that this enzyme is a functional phosphodiesterase. TcrPDEA1 is specific for cAMP with a high Km value (191.1 ± 6.5 μM). Cyclic GMP neither activates the enzyme nor competes as a substrate. In addition, calcium-calmodulin did not affect the kinetic parameters and, as its counterpart in T. brucei, magnesium showed to be crucial for its activity and stability. Although TcrPDEA1 function remains unclear, its presence points out the high complexity of the cAMP signaling in trypanosomatids and the possible compartmentalization of the enzymes involved in the cAMP pathway. © 2006 Elsevier B.V. All rights reserved.

Registro:

Documento: Artículo
Título:TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi
Autor:Alonso, G.D.; Schoijet, A.C.; Torres, H.N.; Flawiá, M.M.
Filiación:Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Fisiología, Biología Molecular y Celular, Vuelta de Obligado 2490, (1428), Buenos Aires, Argentina
Palabras clave:cAMP signaling; Chagas' disease; Kinetoplastids; Phosphodiesterase; calcium; calmodulin; cyclic AMP; cyclic AMP phosphodiesterase; cyclic AMP phosphodiesterase A1; isobutylmethylxanthine; papaverine; phosphodiesterase inhibitor; theophylline; unclassified drug; amino acid sequence; article; controlled study; enzyme activation; enzyme activity; enzyme kinetics; enzyme stability; enzyme substrate; fungal strain; gene frequency; genetic code; kinetoplast; mutant; nonhuman; nucleotide sequence; orthology; priority journal; protein family; protein function; signal transduction; Trypanosoma brucei; Trypanosoma cruzi; 1-Methyl-3-isobutylxanthine; 3',5'-Cyclic-Nucleotide Phosphodiesterase; 5'-Guanylic Acid; Amino Acid Sequence; Animals; Calcium; Calmodulin; Coenzymes; DNA, Protozoan; Enzyme Activators; Enzyme Stability; Gene Dosage; Genetic Complementation Test; Magnesium; Molecular Sequence Data; Papaverine; Phosphodiesterase Inhibitors; Saccharomyces cerevisiae; Sequence Analysis, DNA; Substrate Specificity; Theophylline; Trypanosoma cruzi; Kinetoplastida; Trypanosoma brucei; Trypanosoma cruzi; Trypanosomatidae
Año:2007
Volumen:152
Número:1
Página de inicio:72
Página de fin:79
DOI: http://dx.doi.org/10.1016/j.molbiopara.2006.12.002
Título revista:Molecular and Biochemical Parasitology
Título revista abreviado:Mol. Biochem. Parasitol.
ISSN:01666851
CODEN:MBIPD
CAS:calcium, 7440-70-2; cyclic AMP, 60-92-4; cyclic AMP phosphodiesterase, 9036-21-9; isobutylmethylxanthine, 28822-58-4; papaverine, 58-74-2, 61-25-6; theophylline, 58-55-9, 5967-84-0, 8055-07-0, 8061-56-1, 99007-19-9; 1-Methyl-3-isobutylxanthine, 28822-58-4; 3',5'-Cyclic-Nucleotide Phosphodiesterase, 3.1.4.17; 5'-Guanylic Acid, 85-32-5; Calcium, 7440-70-2; Calmodulin; Coenzymes; DNA, Protozoan; Enzyme Activators; Magnesium, 7439-95-4; Papaverine, 58-74-2; Phosphodiesterase Inhibitors; Theophylline, 58-55-9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01666851_v152_n1_p72_Alonso

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Citas:

---------- APA ----------
Alonso, G.D., Schoijet, A.C., Torres, H.N. & Flawiá, M.M. (2007) . TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi. Molecular and Biochemical Parasitology, 152(1), 72-79.
http://dx.doi.org/10.1016/j.molbiopara.2006.12.002
---------- CHICAGO ----------
Alonso, G.D., Schoijet, A.C., Torres, H.N., Flawiá, M.M. "TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi" . Molecular and Biochemical Parasitology 152, no. 1 (2007) : 72-79.
http://dx.doi.org/10.1016/j.molbiopara.2006.12.002
---------- MLA ----------
Alonso, G.D., Schoijet, A.C., Torres, H.N., Flawiá, M.M. "TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi" . Molecular and Biochemical Parasitology, vol. 152, no. 1, 2007, pp. 72-79.
http://dx.doi.org/10.1016/j.molbiopara.2006.12.002
---------- VANCOUVER ----------
Alonso, G.D., Schoijet, A.C., Torres, H.N., Flawiá, M.M. TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi. Mol. Biochem. Parasitol. 2007;152(1):72-79.
http://dx.doi.org/10.1016/j.molbiopara.2006.12.002