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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2007
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| 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 |
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paper:paper_01666851_v152_n1_p72_Alonso2023-06-08T15:15:58Z TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi 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 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. 2007 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 |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi |
| topic_facet |
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 |
| description |
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. |
| title |
TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi |
| title_short |
TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi |
| title_full |
TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi |
| title_fullStr |
TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi |
| title_full_unstemmed |
TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological properties from Trypanosoma cruzi |
| title_sort |
tcrpdea1, a camp-specific phosphodiesterase with atypical pharmacological properties from trypanosoma cruzi |
| publishDate |
2007 |
| url |
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 |
| _version_ |
1768543988217806848 |