Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase

Autores
Bandini, Giulia; Mariño, Karina Valeria; Sampaio Guther, Maria Lucia; Wernimont, Amy K.; Kuettel, Sabine; Qiu, Wei; Afzal, Shamshad; Kelner, Anna; Hui, Raymond; Ferguson, Michael
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The enzymes phosphomannomutase (PMM), phospho-N-acetylglucosamine mutase (PAGM) and phosphoglucomutase (PGM) reversibly catalyze the transfer of phosphate between the C6 and C1 hydroxyl groups of mannose, N-acetylglucosamine and glucose, respectively. Although genes for a candidate phosphomannomutase and a phospho-N-acetylglucosamine mutase enzymes have been found in the Trypanosoma brucei genome there is, surprisingly, no candidate gene for phosphoglucomutase. The TbPMM and TbPAGM genes were cloned and expressed in Escherichia coli and the TbPMM enzyme was crystallized and its structure solved at 1.85Å resolution. Antibodies to the recombinant proteins localized endogenous TbPMM to glycosomes in the bloodstream form of the parasite while TbPAGM localized to both the cytosol and glycosomes. Both recombinant enzymes were able to interconvert glucose-phosphates, as well as acting on their own definitive substrates. Analysis of sugar nucleotide levels in parasites with TbPMM or TbPAGM knocked down by RNA interference (RNAi) suggests that, in vivo, PGM activity is catalyzed by both enzymes. This is the first example in any organism of PGM activity being completely replaced in this way and it explains why, uniquely, T. brucei has been able to lose its PGM gene. The RNAi data for TbPMM also showed that this is an essential gene for parasite growth.
Fil: Bandini, Giulia. University of Dundee; Reino Unido
Fil: Mariño, Karina Valeria. University of Dundee; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Sampaio Guther, Maria Lucia. University of Dundee; Reino Unido
Fil: Wernimont, Amy K.. University of Toronto; Canadá
Fil: Kuettel, Sabine. University of Dundee; Reino Unido
Fil: Qiu, Wei. University of Toronto; Canadá
Fil: Afzal, Shamshad. University of Dundee; Reino Unido
Fil: Kelner, Anna. University of Dundee; Reino Unido
Fil: Hui, Raymond. University of Toronto; Canadá
Fil: Ferguson, Michael. University of Dundee; Reino Unido
Materia
Phosphomannomutase
Phophoglucomutase Hosphoglucomutase
Phospho-N-Acetylglucosamine Mutase
Trypanosoma Brucei
Sugar Nucleotide Metabolism
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:11336/42071
Acceder
id CONICETDig_ed413bd94d1d59d14e647748ca0d054e
oai_identifier_str oai:ri.conicet.gov.ar:11336/42071
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutaseBandini, GiuliaMariño, Karina ValeriaSampaio Guther, Maria LuciaWernimont, Amy K.Kuettel, SabineQiu, WeiAfzal, ShamshadKelner, AnnaHui, RaymondFerguson, MichaelPhosphomannomutasePhophoglucomutase HosphoglucomutasePhospho-N-Acetylglucosamine MutaseTrypanosoma BruceiSugar Nucleotide Metabolismhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The enzymes phosphomannomutase (PMM), phospho-N-acetylglucosamine mutase (PAGM) and phosphoglucomutase (PGM) reversibly catalyze the transfer of phosphate between the C6 and C1 hydroxyl groups of mannose, N-acetylglucosamine and glucose, respectively. Although genes for a candidate phosphomannomutase and a phospho-N-acetylglucosamine mutase enzymes have been found in the Trypanosoma brucei genome there is, surprisingly, no candidate gene for phosphoglucomutase. The TbPMM and TbPAGM genes were cloned and expressed in Escherichia coli and the TbPMM enzyme was crystallized and its structure solved at 1.85Å resolution. Antibodies to the recombinant proteins localized endogenous TbPMM to glycosomes in the bloodstream form of the parasite while TbPAGM localized to both the cytosol and glycosomes. Both recombinant enzymes were able to interconvert glucose-phosphates, as well as acting on their own definitive substrates. Analysis of sugar nucleotide levels in parasites with TbPMM or TbPAGM knocked down by RNA interference (RNAi) suggests that, in vivo, PGM activity is catalyzed by both enzymes. This is the first example in any organism of PGM activity being completely replaced in this way and it explains why, uniquely, T. brucei has been able to lose its PGM gene. The RNAi data for TbPMM also showed that this is an essential gene for parasite growth.Fil: Bandini, Giulia. University of Dundee; Reino UnidoFil: Mariño, Karina Valeria. University of Dundee; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sampaio Guther, Maria Lucia. University of Dundee; Reino UnidoFil: Wernimont, Amy K.. University of Toronto; CanadáFil: Kuettel, Sabine. University of Dundee; Reino UnidoFil: Qiu, Wei. University of Toronto; CanadáFil: Afzal, Shamshad. University of Dundee; Reino UnidoFil: Kelner, Anna. University of Dundee; Reino UnidoFil: Hui, Raymond. University of Toronto; CanadáFil: Ferguson, Michael. University of Dundee; Reino UnidoWiley Blackwell Publishing, Inc2012-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/42071Bandini, Giulia; Mariño, Karina Valeria; Sampaio Guther, Maria Lucia; Wernimont, Amy K.; Kuettel, Sabine; et al.; Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase; Wiley Blackwell Publishing, Inc; Molecular Microbiology; 85; 3; 7-2012; 513-5340950-382X1365-2958CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2958.2012.08124.xinfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2958.2012.08124.xinfo:eu-repo/semantics/altIdentifier/pmid/22676716info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22676716/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:51Zoai:ri.conicet.gov.ar:11336/42071instacron: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:34982025-09-29 09:38:51.689CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase
title Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase
spellingShingle Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase
Bandini, Giulia
Phosphomannomutase
Phophoglucomutase Hosphoglucomutase
Phospho-N-Acetylglucosamine Mutase
Trypanosoma Brucei
Sugar Nucleotide Metabolism
title_short Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase
title_full Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase
title_fullStr Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase
title_full_unstemmed Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase
title_sort Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase
dc.creator.none.fl_str_mv Bandini, Giulia
Mariño, Karina Valeria
Sampaio Guther, Maria Lucia
Wernimont, Amy K.
Kuettel, Sabine
Qiu, Wei
Afzal, Shamshad
Kelner, Anna
Hui, Raymond
Ferguson, Michael
author Bandini, Giulia
author_facet Bandini, Giulia
Mariño, Karina Valeria
Sampaio Guther, Maria Lucia
Wernimont, Amy K.
Kuettel, Sabine
Qiu, Wei
Afzal, Shamshad
Kelner, Anna
Hui, Raymond
Ferguson, Michael
author_role author
author2 Mariño, Karina Valeria
Sampaio Guther, Maria Lucia
Wernimont, Amy K.
Kuettel, Sabine
Qiu, Wei
Afzal, Shamshad
Kelner, Anna
Hui, Raymond
Ferguson, Michael
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Phosphomannomutase
Phophoglucomutase Hosphoglucomutase
Phospho-N-Acetylglucosamine Mutase
Trypanosoma Brucei
Sugar Nucleotide Metabolism
topic Phosphomannomutase
Phophoglucomutase Hosphoglucomutase
Phospho-N-Acetylglucosamine Mutase
Trypanosoma Brucei
Sugar Nucleotide Metabolism
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The enzymes phosphomannomutase (PMM), phospho-N-acetylglucosamine mutase (PAGM) and phosphoglucomutase (PGM) reversibly catalyze the transfer of phosphate between the C6 and C1 hydroxyl groups of mannose, N-acetylglucosamine and glucose, respectively. Although genes for a candidate phosphomannomutase and a phospho-N-acetylglucosamine mutase enzymes have been found in the Trypanosoma brucei genome there is, surprisingly, no candidate gene for phosphoglucomutase. The TbPMM and TbPAGM genes were cloned and expressed in Escherichia coli and the TbPMM enzyme was crystallized and its structure solved at 1.85Å resolution. Antibodies to the recombinant proteins localized endogenous TbPMM to glycosomes in the bloodstream form of the parasite while TbPAGM localized to both the cytosol and glycosomes. Both recombinant enzymes were able to interconvert glucose-phosphates, as well as acting on their own definitive substrates. Analysis of sugar nucleotide levels in parasites with TbPMM or TbPAGM knocked down by RNA interference (RNAi) suggests that, in vivo, PGM activity is catalyzed by both enzymes. This is the first example in any organism of PGM activity being completely replaced in this way and it explains why, uniquely, T. brucei has been able to lose its PGM gene. The RNAi data for TbPMM also showed that this is an essential gene for parasite growth.
Fil: Bandini, Giulia. University of Dundee; Reino Unido
Fil: Mariño, Karina Valeria. University of Dundee; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Sampaio Guther, Maria Lucia. University of Dundee; Reino Unido
Fil: Wernimont, Amy K.. University of Toronto; Canadá
Fil: Kuettel, Sabine. University of Dundee; Reino Unido
Fil: Qiu, Wei. University of Toronto; Canadá
Fil: Afzal, Shamshad. University of Dundee; Reino Unido
Fil: Kelner, Anna. University of Dundee; Reino Unido
Fil: Hui, Raymond. University of Toronto; Canadá
Fil: Ferguson, Michael. University of Dundee; Reino Unido
description The enzymes phosphomannomutase (PMM), phospho-N-acetylglucosamine mutase (PAGM) and phosphoglucomutase (PGM) reversibly catalyze the transfer of phosphate between the C6 and C1 hydroxyl groups of mannose, N-acetylglucosamine and glucose, respectively. Although genes for a candidate phosphomannomutase and a phospho-N-acetylglucosamine mutase enzymes have been found in the Trypanosoma brucei genome there is, surprisingly, no candidate gene for phosphoglucomutase. The TbPMM and TbPAGM genes were cloned and expressed in Escherichia coli and the TbPMM enzyme was crystallized and its structure solved at 1.85Å resolution. Antibodies to the recombinant proteins localized endogenous TbPMM to glycosomes in the bloodstream form of the parasite while TbPAGM localized to both the cytosol and glycosomes. Both recombinant enzymes were able to interconvert glucose-phosphates, as well as acting on their own definitive substrates. Analysis of sugar nucleotide levels in parasites with TbPMM or TbPAGM knocked down by RNA interference (RNAi) suggests that, in vivo, PGM activity is catalyzed by both enzymes. This is the first example in any organism of PGM activity being completely replaced in this way and it explains why, uniquely, T. brucei has been able to lose its PGM gene. The RNAi data for TbPMM also showed that this is an essential gene for parasite growth.
publishDate 2012
dc.date.none.fl_str_mv 2012-07
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/11336/42071
Bandini, Giulia; Mariño, Karina Valeria; Sampaio Guther, Maria Lucia; Wernimont, Amy K.; Kuettel, Sabine; et al.; Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase; Wiley Blackwell Publishing, Inc; Molecular Microbiology; 85; 3; 7-2012; 513-534
0950-382X
1365-2958
CONICET Digital
CONICET
url http://hdl.handle.net/11336/42071
identifier_str_mv Bandini, Giulia; Mariño, Karina Valeria; Sampaio Guther, Maria Lucia; Wernimont, Amy K.; Kuettel, Sabine; et al.; Phosphoglucomutase is absent in Trypanosoma brucei and redundantly substituted by phosphomannomutase and phospho-N-acetylglucosamine mutase; Wiley Blackwell Publishing, Inc; Molecular Microbiology; 85; 3; 7-2012; 513-534
0950-382X
1365-2958
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://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2958.2012.08124.x
info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2958.2012.08124.x
info:eu-repo/semantics/altIdentifier/pmid/22676716
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22676716/
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
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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
_version_ 1844613228192071680
score 13.070432

Publicaciones similares