Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi

Arginine kinase catalyzes the transphosphorylation between phosphoarginine and ADP. Phosphoarginine is involved in temporal ATP buffering and inorganic phosphate regulation. Trypanosoma cruzi arginine kinase phosphorylates only L‐arginine (specific activity 398.9 mUE‐min−1 mg−1), and is inhibited by...

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Authors: Pereira, Claudio Alejandro; Alonso, Guillermo Daniel; Ivaldi, María Soledad; Bouvier, León Alberto; Torres, Hector Norberto; Flawia, Mirtha Maria
Format: Article
Status:Published version
Publication date:2003
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/43567
Online Access:http://hdl.handle.net/11336/43567
Access Level:Open access
Keyword:Canavanine
Guanidino Kinase
Homoarginine
Phosphagen Kinase
Phosphoarginine
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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author Pereira, Claudio Alejandro
author2 Alonso, Guillermo Daniel
Ivaldi, María Soledad
Bouvier, León Alberto
Torres, Hector Norberto
Flawia, Mirtha Maria
author2_role author
author
author
author
author
author_browse Alonso, Guillermo Daniel
Bouvier, León Alberto
Flawia, Mirtha Maria
Ivaldi, María Soledad
Pereira, Claudio Alejandro
Torres, Hector Norberto
author_facet Pereira, Claudio Alejandro
Alonso, Guillermo Daniel
Ivaldi, María Soledad
Bouvier, León Alberto
Torres, Hector Norberto
Flawia, Mirtha Maria
author_role author
collection CONICET Digital (CONICET)
description Arginine kinase catalyzes the transphosphorylation between phosphoarginine and ADP. Phosphoarginine is involved in temporal ATP buffering and inorganic phosphate regulation. Trypanosoma cruzi arginine kinase phosphorylates only L‐arginine (specific activity 398.9 mUE‐min−1 mg−1), and is inhibited by the arginine analogs, agmatine, canavanine, nitroarginine, and homoarginine. Canavanine and homoarginine also produce a significant inhibition of the epimastigote culture growth (79.7% and 55.8%, respectively). Inhibition constants were calculated for canavanine and homoarginine (7.55 and 6.02 mM, respectively). In addition, two novel guanidino kinase activities were detected in the epimastigote soluble extract. The development of the arginine kinase inhibitors of T. cruzi could be an important feature because the phosphagens biosynthetic pathway in trypanosomatids is different from the one in their mammalian hosts.
eu_rights_str_mv openAccess
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identifier_str_mv Pereira, Claudio Alejandro; Alonso, Guillermo Daniel; Ivaldi, María Soledad; Bouvier, León Alberto; Torres, Hector Norberto; et al.; Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi; Wiley Blackwell Publishing, Inc; Journal of Eukaryotic Microbiology; 50; 2; 12-2003; 132-134
1066-5234
CONICET Digital
CONICET
institution Consejo Nacional de Investigaciones Científicas y Técnicas
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
language eng
network_acronym_str AR
network_name_str Argentina
oai_identifier_str oai:ri.conicet.gov.ar:11336/43567
publishDate 2003
publishDateSort 2003
publisher Wiley Blackwell Publishing, Inc
publisherStr Wiley Blackwell Publishing, Inc
reponame_str CONICET Digital (CONICET)
spelling Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi Pereira, Claudio Alejandro Alonso, Guillermo Daniel Ivaldi, María Soledad Bouvier, León Alberto Torres, Hector Norberto Flawia, Mirtha Maria Canavanine Guanidino Kinase Homoarginine Phosphagen Kinase Phosphoarginine https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 Arginine kinase catalyzes the transphosphorylation between phosphoarginine and ADP. Phosphoarginine is involved in temporal ATP buffering and inorganic phosphate regulation. Trypanosoma cruzi arginine kinase phosphorylates only L‐arginine (specific activity 398.9 mUE‐min−1 mg−1), and is inhibited by the arginine analogs, agmatine, canavanine, nitroarginine, and homoarginine. Canavanine and homoarginine also produce a significant inhibition of the epimastigote culture growth (79.7% and 55.8%, respectively). Inhibition constants were calculated for canavanine and homoarginine (7.55 and 6.02 mM, respectively). In addition, two novel guanidino kinase activities were detected in the epimastigote soluble extract. The development of the arginine kinase inhibitors of T. cruzi could be an important feature because the phosphagens biosynthetic pathway in trypanosomatids is different from the one in their mammalian hosts. Fil: Pereira, Claudio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Alonso, Guillermo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Ivaldi, María Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Bouvier, León Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Torres, Hector Norberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Flawia, Mirtha Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Wiley Blackwell Publishing, Inc http://hdl.handle.net/11336/43567 Pereira, Claudio Alejandro; Alonso, Guillermo Daniel; Ivaldi, María Soledad; Bouvier, León Alberto; Torres, Hector Norberto; et al.; Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi; Wiley Blackwell Publishing, Inc; Journal of Eukaryotic Microbiology; 50; 2; 12-2003; 132-134 1066-5234 CONICET Digital CONICET
spellingShingle Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi
Pereira, Claudio Alejandro
Canavanine
Guanidino Kinase
Homoarginine
Phosphagen Kinase
Phosphoarginine
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
status_str publishedVersion
title Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi
title_full Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi
title_fullStr Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi
title_full_unstemmed Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi
title_short Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi
title_sort Screening of Substrate Analogs as Potential Enzyme Inhibitors for the Arginine Kinase of Trypanosoma cruzi
topic Canavanine
Guanidino Kinase
Homoarginine
Phosphagen Kinase
Phosphoarginine
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic_facet Canavanine
Guanidino Kinase
Homoarginine
Phosphagen Kinase
Phosphoarginine
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
url http://hdl.handle.net/11336/43567