Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.

Autores
Giordana, Lucila; Suárez Mantilla, Brian; Santana, Marianela; Silber, Ariel Mariano; Nowicki, Cristina
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Leishmania parasites seem capable of producing cysteine by de novo biosynthesis, similarly to bacteria, some pathogenic protists, and plants. In Leishmania spp., cysteine synthase (CS) and cystathionine β-synthase (CBS) are expected to participate in this metabolic process. Moreover, the reverse transsulfuration pathway (RTP) is also predicted to be operative in this trypanosomatid because CBS also catalyzes the condensation of serine with homocysteine, and a gene encoding a putative cystathionine γ-lyase (CGL) is present in all the sequenced genomes. Our results show that indeed, Leishmania major CGL is able to rescue the wild-type phenotype of a Saccharomyces cerevisiae CGL-null mutant and is susceptible to inhibition by an irreversible CGL inhibitor, DL-propargylglycine (PAG). In Leishmania promastigotes, CGL and CS are cytosolic enzymes. The coexistence of de novo synthesis with the RTP is extremely rare in most living organisms; however, despite this potentially high redundancy in cysteine production, PAG arrests the proliferation of L. major promastigotes with an IC50 of approximately 65 μM. These findings raise new questions regarding the biological role of CGL in these pathogens and indicate the need for understanding the molecular mechanism of PAG action in vivo to identify the potential targets affected by this drug.
Fil: Giordana, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Suárez Mantilla, Brian. Universidade de Sao Paulo; Brasil
Fil: Santana, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Silber, Ariel Mariano. Universidade de Sao Paulo; Brasil
Fil: Nowicki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Materia
Leishmania Parasites
Dl-Propargylglycine
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:11336/32287
Acceder
id CONICETDig_7978505f9720dc356925d7c0101c1808
oai_identifier_str oai:ri.conicet.gov.ar:11336/32287
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.Giordana, LucilaSuárez Mantilla, BrianSantana, MarianelaSilber, Ariel MarianoNowicki, CristinaLeishmania ParasitesDl-Propargylglycinehttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Leishmania parasites seem capable of producing cysteine by de novo biosynthesis, similarly to bacteria, some pathogenic protists, and plants. In Leishmania spp., cysteine synthase (CS) and cystathionine β-synthase (CBS) are expected to participate in this metabolic process. Moreover, the reverse transsulfuration pathway (RTP) is also predicted to be operative in this trypanosomatid because CBS also catalyzes the condensation of serine with homocysteine, and a gene encoding a putative cystathionine γ-lyase (CGL) is present in all the sequenced genomes. Our results show that indeed, Leishmania major CGL is able to rescue the wild-type phenotype of a Saccharomyces cerevisiae CGL-null mutant and is susceptible to inhibition by an irreversible CGL inhibitor, DL-propargylglycine (PAG). In Leishmania promastigotes, CGL and CS are cytosolic enzymes. The coexistence of de novo synthesis with the RTP is extremely rare in most living organisms; however, despite this potentially high redundancy in cysteine production, PAG arrests the proliferation of L. major promastigotes with an IC50 of approximately 65 μM. These findings raise new questions regarding the biological role of CGL in these pathogens and indicate the need for understanding the molecular mechanism of PAG action in vivo to identify the potential targets affected by this drug.Fil: Giordana, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Suárez Mantilla, Brian. Universidade de Sao Paulo; BrasilFil: Santana, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Silber, Ariel Mariano. Universidade de Sao Paulo; BrasilFil: Nowicki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaWiley Blackwell Publishing, Inc2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/32287Nowicki, Cristina; Silber, Ariel Mariano; Santana, Marianela; Suárez Mantilla, Brian; Giordana, Lucila; Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.; Wiley Blackwell Publishing, Inc; Journal of Eukaryotic Microbiology; 61; 2; 3-2014; 204-2131066-5234CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/jeu.12100/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/jeu.12100info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:57:43Zoai:ri.conicet.gov.ar:11336/32287instacron: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 09:57:43.905CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.
title Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.
spellingShingle Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.
Giordana, Lucila
Leishmania Parasites
Dl-Propargylglycine
title_short Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.
title_full Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.
title_fullStr Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.
title_full_unstemmed Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.
title_sort Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.
dc.creator.none.fl_str_mv Giordana, Lucila
Suárez Mantilla, Brian
Santana, Marianela
Silber, Ariel Mariano
Nowicki, Cristina
author Giordana, Lucila
author_facet Giordana, Lucila
Suárez Mantilla, Brian
Santana, Marianela
Silber, Ariel Mariano
Nowicki, Cristina
author_role author
author2 Suárez Mantilla, Brian
Santana, Marianela
Silber, Ariel Mariano
Nowicki, Cristina
author2_role author
author
author
author
dc.subject.none.fl_str_mv Leishmania Parasites
Dl-Propargylglycine
topic Leishmania Parasites
Dl-Propargylglycine
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Leishmania parasites seem capable of producing cysteine by de novo biosynthesis, similarly to bacteria, some pathogenic protists, and plants. In Leishmania spp., cysteine synthase (CS) and cystathionine β-synthase (CBS) are expected to participate in this metabolic process. Moreover, the reverse transsulfuration pathway (RTP) is also predicted to be operative in this trypanosomatid because CBS also catalyzes the condensation of serine with homocysteine, and a gene encoding a putative cystathionine γ-lyase (CGL) is present in all the sequenced genomes. Our results show that indeed, Leishmania major CGL is able to rescue the wild-type phenotype of a Saccharomyces cerevisiae CGL-null mutant and is susceptible to inhibition by an irreversible CGL inhibitor, DL-propargylglycine (PAG). In Leishmania promastigotes, CGL and CS are cytosolic enzymes. The coexistence of de novo synthesis with the RTP is extremely rare in most living organisms; however, despite this potentially high redundancy in cysteine production, PAG arrests the proliferation of L. major promastigotes with an IC50 of approximately 65 μM. These findings raise new questions regarding the biological role of CGL in these pathogens and indicate the need for understanding the molecular mechanism of PAG action in vivo to identify the potential targets affected by this drug.
Fil: Giordana, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Suárez Mantilla, Brian. Universidade de Sao Paulo; Brasil
Fil: Santana, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Silber, Ariel Mariano. Universidade de Sao Paulo; Brasil
Fil: Nowicki, Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
description Leishmania parasites seem capable of producing cysteine by de novo biosynthesis, similarly to bacteria, some pathogenic protists, and plants. In Leishmania spp., cysteine synthase (CS) and cystathionine β-synthase (CBS) are expected to participate in this metabolic process. Moreover, the reverse transsulfuration pathway (RTP) is also predicted to be operative in this trypanosomatid because CBS also catalyzes the condensation of serine with homocysteine, and a gene encoding a putative cystathionine γ-lyase (CGL) is present in all the sequenced genomes. Our results show that indeed, Leishmania major CGL is able to rescue the wild-type phenotype of a Saccharomyces cerevisiae CGL-null mutant and is susceptible to inhibition by an irreversible CGL inhibitor, DL-propargylglycine (PAG). In Leishmania promastigotes, CGL and CS are cytosolic enzymes. The coexistence of de novo synthesis with the RTP is extremely rare in most living organisms; however, despite this potentially high redundancy in cysteine production, PAG arrests the proliferation of L. major promastigotes with an IC50 of approximately 65 μM. These findings raise new questions regarding the biological role of CGL in these pathogens and indicate the need for understanding the molecular mechanism of PAG action in vivo to identify the potential targets affected by this drug.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
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/11336/32287
Nowicki, Cristina; Silber, Ariel Mariano; Santana, Marianela; Suárez Mantilla, Brian; Giordana, Lucila; Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.; Wiley Blackwell Publishing, Inc; Journal of Eukaryotic Microbiology; 61; 2; 3-2014; 204-213
1066-5234
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32287
identifier_str_mv Nowicki, Cristina; Silber, Ariel Mariano; Santana, Marianela; Suárez Mantilla, Brian; Giordana, Lucila; Cystathionine γ-lyase, an Enzyme Related to the Reverse Transsulfuration Pathway, is Functional in Leishmania spp.; Wiley Blackwell Publishing, Inc; Journal of Eukaryotic Microbiology; 61; 2; 3-2014; 204-213
1066-5234
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/jeu.12100/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/jeu.12100
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
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_ 1842269480223244288
score 13.13397

Publicaciones similares