Exploring protein myristoylation in Toxoplasma gondii

Autores
Alonso, Andrés Mariano; Turowski, Valeria Rosana; Ruiz, Diego Mario; Orelo, Barbara D.; Moresco, James J.; Yates, John R.; Corvi, Maria Martha
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Toxoplasma gondii is an important human and veterinary pathogen and the causative agent of toxoplasmosis, a potentially severe disease especially in immunocompromised or congenitally infected humans. Current therapeutic compounds are not well-tolerated, present increasing resistance, limited efficacy and require long periods of treatment. On this context, searching for new therapeutic targets is crucial to drug discovery. In this sense, recent works suggest that N-myristoyltransferase (NMT), the enzyme responsible for protein myristoylation that is essential in some parasites, could be the target of new anti-parasitic compounds. However, up to date there is no information on NMT and the extent of this modification in T. gondii. In this work, we decided to explore T. gondii genome in search of elements related with the N-myristoylation process. By a bioinformatics approach it was possible to identify a putative T. gondii NMT (TgNMT). This enzyme that is homologous to other parasitic NMTs, presents activity in vitro, is expressed in both intra- and extracellular parasites and interacts with predicted TgNMT substrates. Additionally, NMT activity seems to be important for the lytic cycle of Toxoplasma gondii. In parallel, an in silico myristoylome predicts 157 proteins to be affected by this modification. Myristoylated proteins would be affecting several metabolic functions with some of them being critical for the life cycle of this parasite. Together, these data indicate that TgNMT could be an interesting target of intervention for the treatment of toxoplasmosis.
Fil: Alonso, Andrés Mariano. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; Argentina. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina
Fil: Turowski, Valeria Rosana. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Ruiz, Diego Mario. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Orelo, Barbara D.. The Scripps Research Institute; Estados Unidos
Fil: Moresco, James J.. The Scripps Research Institute; Estados Unidos
Fil: Yates, John R.. The Scripps Research Institute; Estados Unidos
Fil: Corvi, Maria Martha. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; Argentina
Materia
CALCIUM HOMEOSTASIS
MYRISTOYLOME
N-MYRISTOYLTRANSFERASE
PROTEIN MYRISTOYLATION
TOXOPLASMA GONDII
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/127853
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/127853
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Exploring protein myristoylation in Toxoplasma gondiiAlonso, Andrés MarianoTurowski, Valeria RosanaRuiz, Diego MarioOrelo, Barbara D.Moresco, James J.Yates, John R.Corvi, Maria MarthaCALCIUM HOMEOSTASISMYRISTOYLOMEN-MYRISTOYLTRANSFERASEPROTEIN MYRISTOYLATIONTOXOPLASMA GONDIIhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Toxoplasma gondii is an important human and veterinary pathogen and the causative agent of toxoplasmosis, a potentially severe disease especially in immunocompromised or congenitally infected humans. Current therapeutic compounds are not well-tolerated, present increasing resistance, limited efficacy and require long periods of treatment. On this context, searching for new therapeutic targets is crucial to drug discovery. In this sense, recent works suggest that N-myristoyltransferase (NMT), the enzyme responsible for protein myristoylation that is essential in some parasites, could be the target of new anti-parasitic compounds. However, up to date there is no information on NMT and the extent of this modification in T. gondii. In this work, we decided to explore T. gondii genome in search of elements related with the N-myristoylation process. By a bioinformatics approach it was possible to identify a putative T. gondii NMT (TgNMT). This enzyme that is homologous to other parasitic NMTs, presents activity in vitro, is expressed in both intra- and extracellular parasites and interacts with predicted TgNMT substrates. Additionally, NMT activity seems to be important for the lytic cycle of Toxoplasma gondii. In parallel, an in silico myristoylome predicts 157 proteins to be affected by this modification. Myristoylated proteins would be affecting several metabolic functions with some of them being critical for the life cycle of this parasite. Together, these data indicate that TgNMT could be an interesting target of intervention for the treatment of toxoplasmosis.Fil: Alonso, Andrés Mariano. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; Argentina. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; ArgentinaFil: Turowski, Valeria Rosana. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Ruiz, Diego Mario. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Orelo, Barbara D.. The Scripps Research Institute; Estados UnidosFil: Moresco, James J.. The Scripps Research Institute; Estados UnidosFil: Yates, John R.. The Scripps Research Institute; Estados UnidosFil: Corvi, Maria Martha. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; ArgentinaAcademic Press Inc Elsevier Science2019-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/127853Alonso, Andrés Mariano; Turowski, Valeria Rosana; Ruiz, Diego Mario; Orelo, Barbara D.; Moresco, James J.; et al.; Exploring protein myristoylation in Toxoplasma gondii; Academic Press Inc Elsevier Science; Experimental Parasitology; 203; 8-2019; 8-180014-4894CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0014489419300086info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2019.05.007info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:06:27Zoai:ri.conicet.gov.ar:11336/127853instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:06:27.463CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Exploring protein myristoylation in Toxoplasma gondii
title Exploring protein myristoylation in Toxoplasma gondii
spellingShingle Exploring protein myristoylation in Toxoplasma gondii
Alonso, Andrés Mariano
CALCIUM HOMEOSTASIS
MYRISTOYLOME
N-MYRISTOYLTRANSFERASE
PROTEIN MYRISTOYLATION
TOXOPLASMA GONDII
title_short Exploring protein myristoylation in Toxoplasma gondii
title_full Exploring protein myristoylation in Toxoplasma gondii
title_fullStr Exploring protein myristoylation in Toxoplasma gondii
title_full_unstemmed Exploring protein myristoylation in Toxoplasma gondii
title_sort Exploring protein myristoylation in Toxoplasma gondii
dc.creator.none.fl_str_mv Alonso, Andrés Mariano
Turowski, Valeria Rosana
Ruiz, Diego Mario
Orelo, Barbara D.
Moresco, James J.
Yates, John R.
Corvi, Maria Martha
author Alonso, Andrés Mariano
author_facet Alonso, Andrés Mariano
Turowski, Valeria Rosana
Ruiz, Diego Mario
Orelo, Barbara D.
Moresco, James J.
Yates, John R.
Corvi, Maria Martha
author_role author
author2 Turowski, Valeria Rosana
Ruiz, Diego Mario
Orelo, Barbara D.
Moresco, James J.
Yates, John R.
Corvi, Maria Martha
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CALCIUM HOMEOSTASIS
MYRISTOYLOME
N-MYRISTOYLTRANSFERASE
PROTEIN MYRISTOYLATION
TOXOPLASMA GONDII
topic CALCIUM HOMEOSTASIS
MYRISTOYLOME
N-MYRISTOYLTRANSFERASE
PROTEIN MYRISTOYLATION
TOXOPLASMA GONDII
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Toxoplasma gondii is an important human and veterinary pathogen and the causative agent of toxoplasmosis, a potentially severe disease especially in immunocompromised or congenitally infected humans. Current therapeutic compounds are not well-tolerated, present increasing resistance, limited efficacy and require long periods of treatment. On this context, searching for new therapeutic targets is crucial to drug discovery. In this sense, recent works suggest that N-myristoyltransferase (NMT), the enzyme responsible for protein myristoylation that is essential in some parasites, could be the target of new anti-parasitic compounds. However, up to date there is no information on NMT and the extent of this modification in T. gondii. In this work, we decided to explore T. gondii genome in search of elements related with the N-myristoylation process. By a bioinformatics approach it was possible to identify a putative T. gondii NMT (TgNMT). This enzyme that is homologous to other parasitic NMTs, presents activity in vitro, is expressed in both intra- and extracellular parasites and interacts with predicted TgNMT substrates. Additionally, NMT activity seems to be important for the lytic cycle of Toxoplasma gondii. In parallel, an in silico myristoylome predicts 157 proteins to be affected by this modification. Myristoylated proteins would be affecting several metabolic functions with some of them being critical for the life cycle of this parasite. Together, these data indicate that TgNMT could be an interesting target of intervention for the treatment of toxoplasmosis.
Fil: Alonso, Andrés Mariano. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; Argentina. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina
Fil: Turowski, Valeria Rosana. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Ruiz, Diego Mario. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Orelo, Barbara D.. The Scripps Research Institute; Estados Unidos
Fil: Moresco, James J.. The Scripps Research Institute; Estados Unidos
Fil: Yates, John R.. The Scripps Research Institute; Estados Unidos
Fil: Corvi, Maria Martha. Universidad Nacional de San Martin. Instituto Tecnológico de Chascomús - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Tecnológico de Chascomús; Argentina
description Toxoplasma gondii is an important human and veterinary pathogen and the causative agent of toxoplasmosis, a potentially severe disease especially in immunocompromised or congenitally infected humans. Current therapeutic compounds are not well-tolerated, present increasing resistance, limited efficacy and require long periods of treatment. On this context, searching for new therapeutic targets is crucial to drug discovery. In this sense, recent works suggest that N-myristoyltransferase (NMT), the enzyme responsible for protein myristoylation that is essential in some parasites, could be the target of new anti-parasitic compounds. However, up to date there is no information on NMT and the extent of this modification in T. gondii. In this work, we decided to explore T. gondii genome in search of elements related with the N-myristoylation process. By a bioinformatics approach it was possible to identify a putative T. gondii NMT (TgNMT). This enzyme that is homologous to other parasitic NMTs, presents activity in vitro, is expressed in both intra- and extracellular parasites and interacts with predicted TgNMT substrates. Additionally, NMT activity seems to be important for the lytic cycle of Toxoplasma gondii. In parallel, an in silico myristoylome predicts 157 proteins to be affected by this modification. Myristoylated proteins would be affecting several metabolic functions with some of them being critical for the life cycle of this parasite. Together, these data indicate that TgNMT could be an interesting target of intervention for the treatment of toxoplasmosis.
publishDate 2019
dc.date.none.fl_str_mv 2019-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/127853
Alonso, Andrés Mariano; Turowski, Valeria Rosana; Ruiz, Diego Mario; Orelo, Barbara D.; Moresco, James J.; et al.; Exploring protein myristoylation in Toxoplasma gondii; Academic Press Inc Elsevier Science; Experimental Parasitology; 203; 8-2019; 8-18
0014-4894
CONICET Digital
CONICET
url http://hdl.handle.net/11336/127853
identifier_str_mv Alonso, Andrés Mariano; Turowski, Valeria Rosana; Ruiz, Diego Mario; Orelo, Barbara D.; Moresco, James J.; et al.; Exploring protein myristoylation in Toxoplasma gondii; Academic Press Inc Elsevier Science; Experimental Parasitology; 203; 8-2019; 8-18
0014-4894
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0014489419300086
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2019.05.007
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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