A single NMT is relevant for Toxoplasma gondii lytic cycle

Autores
Alonso, A. M.; Turowski, Valeria Rosana; Ruiz, Diego Mario; Orelo, B. D.; Moresco, J. J.; Yates, J. R.; Corvi, Maria Martha
Año de publicación
2018
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Toxoplasma gondii is the causative agent of toxoplasmosis. This disease affects almost one third of the world's population with devastating effects. Despite the significant progress that has been made in order to develop new compounds to treat toxoplasmosis, the current therapeutic agents frequently used have toxic side effects. As such, scientists are in real need of finding new targets of intervention. Protein myristoylation is a post- and co-translational modification that affects a variety of proteins in many cells including parasites. It is catalyzed by N-myristoyltranferase (NMT), a conserved enzyme that has been described to be essential in many protozoan pathogens. However, up to date, there is scarce information on NMT and the extent of this modification in T. gondii. In this work T. gondii NMT (TgNMT) was identified and characterized. Structural analyses suggest that there are differences between human and T. gondii NMTs, which could be of importance to design specific inhibitors. Furthermore, this protein presents NMT activity in vitro, is expressed in both intra- and extracellular parasites and interacts with predicted TgNMT substrates. Additionally, TgNMT activity seems to be important for the lytic cycle. An in silico myristoylome predicts 157 proteins to be targeted by this modification with some of them being critical for the life cycle of this parasite. This analysis suggests that myristoylation could be regulating calcium homeostasis which is critical for T. gondii pathogenesis. Together, these data indicate that TgNMT could be an interesting target of intervention for the treatment of toxoplasmosis.
Fil: Alonso, A. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Turowski, Valeria Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Ruiz, Diego Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Orelo, B. D.. The Scripps Research Institute; Estados Unidos
Fil: Moresco, J. J.. The Scripps Research Institute; Estados Unidos
Fil: Yates, J. R.. The Scripps Research Institute; Estados Unidos
Fil: Corvi, Maria Martha. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
LIV Annual Meeting- Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular (SAIB)
Paraná
Argentina
Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular
Materia
TOXOPLASMA GONDII
MYRISTOYLATION
MYRISTOYLOME
NMT
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:11336/250633
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/250633
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A single NMT is relevant for Toxoplasma gondii lytic cycleAlonso, A. M.Turowski, Valeria RosanaRuiz, Diego MarioOrelo, B. D.Moresco, J. J.Yates, J. R.Corvi, Maria MarthaTOXOPLASMA GONDIIMYRISTOYLATIONMYRISTOYLOMENMThttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Toxoplasma gondii is the causative agent of toxoplasmosis. This disease affects almost one third of the world's population with devastating effects. Despite the significant progress that has been made in order to develop new compounds to treat toxoplasmosis, the current therapeutic agents frequently used have toxic side effects. As such, scientists are in real need of finding new targets of intervention. Protein myristoylation is a post- and co-translational modification that affects a variety of proteins in many cells including parasites. It is catalyzed by N-myristoyltranferase (NMT), a conserved enzyme that has been described to be essential in many protozoan pathogens. However, up to date, there is scarce information on NMT and the extent of this modification in T. gondii. In this work T. gondii NMT (TgNMT) was identified and characterized. Structural analyses suggest that there are differences between human and T. gondii NMTs, which could be of importance to design specific inhibitors. Furthermore, this protein presents NMT activity in vitro, is expressed in both intra- and extracellular parasites and interacts with predicted TgNMT substrates. Additionally, TgNMT activity seems to be important for the lytic cycle. An in silico myristoylome predicts 157 proteins to be targeted by this modification with some of them being critical for the life cycle of this parasite. This analysis suggests that myristoylation could be regulating calcium homeostasis which is critical for T. gondii pathogenesis. Together, these data indicate that TgNMT could be an interesting target of intervention for the treatment of toxoplasmosis.Fil: Alonso, A. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Turowski, Valeria Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Ruiz, Diego Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Orelo, B. D.. The Scripps Research Institute; Estados UnidosFil: Moresco, J. J.. The Scripps Research Institute; Estados UnidosFil: Yates, J. R.. The Scripps Research Institute; Estados UnidosFil: Corvi, Maria Martha. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaLIV Annual Meeting- Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular (SAIB)ParanáArgentinaSociedad Argentina de investigaciones Bioquimicas y Biologia MolecularSociedad Argentina de investigaciones Bioquimicas y Biologia Molecular2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/250633A single NMT is relevant for Toxoplasma gondii lytic cycle; LIV Annual Meeting- Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular (SAIB); Paraná; Argentina; 2018; 75-751667-5746CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://saib.org.ar/publicaciones/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:45:37Zoai:ri.conicet.gov.ar:11336/250633instacron: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 09:45:37.878CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A single NMT is relevant for Toxoplasma gondii lytic cycle
title A single NMT is relevant for Toxoplasma gondii lytic cycle
spellingShingle A single NMT is relevant for Toxoplasma gondii lytic cycle
Alonso, A. M.
TOXOPLASMA GONDII
MYRISTOYLATION
MYRISTOYLOME
NMT
title_short A single NMT is relevant for Toxoplasma gondii lytic cycle
title_full A single NMT is relevant for Toxoplasma gondii lytic cycle
title_fullStr A single NMT is relevant for Toxoplasma gondii lytic cycle
title_full_unstemmed A single NMT is relevant for Toxoplasma gondii lytic cycle
title_sort A single NMT is relevant for Toxoplasma gondii lytic cycle
dc.creator.none.fl_str_mv Alonso, A. M.
Turowski, Valeria Rosana
Ruiz, Diego Mario
Orelo, B. D.
Moresco, J. J.
Yates, J. R.
Corvi, Maria Martha
author Alonso, A. M.
author_facet Alonso, A. M.
Turowski, Valeria Rosana
Ruiz, Diego Mario
Orelo, B. D.
Moresco, J. J.
Yates, J. R.
Corvi, Maria Martha
author_role author
author2 Turowski, Valeria Rosana
Ruiz, Diego Mario
Orelo, B. D.
Moresco, J. J.
Yates, J. R.
Corvi, Maria Martha
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv TOXOPLASMA GONDII
MYRISTOYLATION
MYRISTOYLOME
NMT
topic TOXOPLASMA GONDII
MYRISTOYLATION
MYRISTOYLOME
NMT
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 the causative agent of toxoplasmosis. This disease affects almost one third of the world's population with devastating effects. Despite the significant progress that has been made in order to develop new compounds to treat toxoplasmosis, the current therapeutic agents frequently used have toxic side effects. As such, scientists are in real need of finding new targets of intervention. Protein myristoylation is a post- and co-translational modification that affects a variety of proteins in many cells including parasites. It is catalyzed by N-myristoyltranferase (NMT), a conserved enzyme that has been described to be essential in many protozoan pathogens. However, up to date, there is scarce information on NMT and the extent of this modification in T. gondii. In this work T. gondii NMT (TgNMT) was identified and characterized. Structural analyses suggest that there are differences between human and T. gondii NMTs, which could be of importance to design specific inhibitors. Furthermore, this protein presents NMT activity in vitro, is expressed in both intra- and extracellular parasites and interacts with predicted TgNMT substrates. Additionally, TgNMT activity seems to be important for the lytic cycle. An in silico myristoylome predicts 157 proteins to be targeted by this modification with some of them being critical for the life cycle of this parasite. This analysis suggests that myristoylation could be regulating calcium homeostasis which is critical for T. gondii pathogenesis. Together, these data indicate that TgNMT could be an interesting target of intervention for the treatment of toxoplasmosis.
Fil: Alonso, A. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Turowski, Valeria Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Ruiz, Diego Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Orelo, B. D.. The Scripps Research Institute; Estados Unidos
Fil: Moresco, J. J.. The Scripps Research Institute; Estados Unidos
Fil: Yates, J. R.. The Scripps Research Institute; Estados Unidos
Fil: Corvi, Maria Martha. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
LIV Annual Meeting- Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular (SAIB)
Paraná
Argentina
Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular
description Toxoplasma gondii is the causative agent of toxoplasmosis. This disease affects almost one third of the world's population with devastating effects. Despite the significant progress that has been made in order to develop new compounds to treat toxoplasmosis, the current therapeutic agents frequently used have toxic side effects. As such, scientists are in real need of finding new targets of intervention. Protein myristoylation is a post- and co-translational modification that affects a variety of proteins in many cells including parasites. It is catalyzed by N-myristoyltranferase (NMT), a conserved enzyme that has been described to be essential in many protozoan pathogens. However, up to date, there is scarce information on NMT and the extent of this modification in T. gondii. In this work T. gondii NMT (TgNMT) was identified and characterized. Structural analyses suggest that there are differences between human and T. gondii NMTs, which could be of importance to design specific inhibitors. Furthermore, this protein presents NMT activity in vitro, is expressed in both intra- and extracellular parasites and interacts with predicted TgNMT substrates. Additionally, TgNMT activity seems to be important for the lytic cycle. An in silico myristoylome predicts 157 proteins to be targeted by this modification with some of them being critical for the life cycle of this parasite. This analysis suggests that myristoylation could be regulating calcium homeostasis which is critical for T. gondii pathogenesis. Together, these data indicate that TgNMT could be an interesting target of intervention for the treatment of toxoplasmosis.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/250633
A single NMT is relevant for Toxoplasma gondii lytic cycle; LIV Annual Meeting- Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular (SAIB); Paraná; Argentina; 2018; 75-75
1667-5746
CONICET Digital
CONICET
url http://hdl.handle.net/11336/250633
identifier_str_mv A single NMT is relevant for Toxoplasma gondii lytic cycle; LIV Annual Meeting- Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular (SAIB); Paraná; Argentina; 2018; 75-75
1667-5746
CONICET Digital
CONICET
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language eng
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dc.publisher.none.fl_str_mv Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular
publisher.none.fl_str_mv Sociedad Argentina de investigaciones Bioquimicas y Biologia Molecular
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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