TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi

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 cAM...

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Guardado en:
Detalles Bibliográficos
Publicado: 2007
Materias:
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
Kinetoplastida
Trypanosomatidae
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01666851_v152_n1_p72_Alonso
http://hdl.handle.net/20.500.12110/paper_01666851_v152_n1_p72_Alonso
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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.

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