First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera

Autores
Agüero, Facundo Ariel; Maglioco, Andrea Florencia; Valacco, Maria Pia; Juarez Valdez, Alejandra Yaqueline; Roldán, Emilio; Paulino, Margot; Fuchs, Alicia Graciela
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cystic echinococcosis (CE) is an endemic zoonotic disease caused by Echinococcus granulosus, which forms cysts in ungulates’ intermediate hosts. Humans are accidental hosts, and CE affects more than one million people worldwide. Imaging remains the diagnostic gold standard, outperforming serological methods. This study presents an in silico analysis of two glyceraldehyde-3-phosphate dehydrogenase (GAPDH) isoenzymes from E. granulosus (EgGAPDH), isolated from a parasite cell line (EGPE). EgGAPDHs were recognized by sera from CE patients, identified through LC-MS/MS and PCR of metacestodes from cattle liver. One isoenzyme is intracellular (IC) (UniProt: W6UJ19), and the other is extracellular (EC) (UniProt: W6V1T8). GAPDH is involved in host–parasite interactions and metabolic processes. We characterized the physicochemical properties; linear epitopes (LEPs); and amino acid domains of EgGAPDH, its hosts, and other parasites. W6UJ19 emerged as the most promising isoenzyme as a marker of infection. Molecular dynamics simulations of isoenzymes, performed in the presence or absence of two bisphosphonates (BPs), revealed how drug binding alters conformational epitopes (CEPs) and suggested that W6UJ19 is more responsive to BP modulation. Binding affinity analysis using the MMPBSA method revealed that etidronate (EHDP) binds EgGAPDH with greater affinity than phosphate (Pi) and alendronate (AL), in the following order: EHDP > Pi > AL.
Fil: Agüero, Facundo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; Argentina
Fil: Maglioco, Andrea Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; Argentina
Fil: Valacco, Maria Pia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Juarez Valdez, Alejandra Yaqueline. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roldán, Emilio. Universidad Abierta Interamericana; Argentina
Fil: Paulino, Margot. Universidad de la República; Uruguay
Fil: Fuchs, Alicia Graciela. Universidad Abierta Interamericana; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina
Materia
glyceraldehyde 3 phosphate dehydrogenase
in silico analysis
Echinococcus granulosus
molecular dynamics simulation
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:11336/282023
Acceder
id CONICETDig_9649361b8a7d6b72993dfe128ae3fad1
oai_identifier_str oai:ri.conicet.gov.ar:11336/282023
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human SeraAgüero, Facundo ArielMaglioco, Andrea FlorenciaValacco, Maria PiaJuarez Valdez, Alejandra YaquelineRoldán, EmilioPaulino, MargotFuchs, Alicia Gracielaglyceraldehyde 3 phosphate dehydrogenasein silico analysisEchinococcus granulosusmolecular dynamics simulationhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.2https://purl.org/becyt/ford/1Cystic echinococcosis (CE) is an endemic zoonotic disease caused by Echinococcus granulosus, which forms cysts in ungulates’ intermediate hosts. Humans are accidental hosts, and CE affects more than one million people worldwide. Imaging remains the diagnostic gold standard, outperforming serological methods. This study presents an in silico analysis of two glyceraldehyde-3-phosphate dehydrogenase (GAPDH) isoenzymes from E. granulosus (EgGAPDH), isolated from a parasite cell line (EGPE). EgGAPDHs were recognized by sera from CE patients, identified through LC-MS/MS and PCR of metacestodes from cattle liver. One isoenzyme is intracellular (IC) (UniProt: W6UJ19), and the other is extracellular (EC) (UniProt: W6V1T8). GAPDH is involved in host–parasite interactions and metabolic processes. We characterized the physicochemical properties; linear epitopes (LEPs); and amino acid domains of EgGAPDH, its hosts, and other parasites. W6UJ19 emerged as the most promising isoenzyme as a marker of infection. Molecular dynamics simulations of isoenzymes, performed in the presence or absence of two bisphosphonates (BPs), revealed how drug binding alters conformational epitopes (CEPs) and suggested that W6UJ19 is more responsive to BP modulation. Binding affinity analysis using the MMPBSA method revealed that etidronate (EHDP) binds EgGAPDH with greater affinity than phosphate (Pi) and alendronate (AL), in the following order: EHDP > Pi > AL.Fil: Agüero, Facundo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; ArgentinaFil: Maglioco, Andrea Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; ArgentinaFil: Valacco, Maria Pia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Juarez Valdez, Alejandra Yaqueline. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Roldán, Emilio. Universidad Abierta Interamericana; ArgentinaFil: Paulino, Margot. Universidad de la República; UruguayFil: Fuchs, Alicia Graciela. Universidad Abierta Interamericana; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; ArgentinaMolecular Diversity Preservation International2025-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/282023Agüero, Facundo Ariel; Maglioco, Andrea Florencia; Valacco, Maria Pia; Juarez Valdez, Alejandra Yaqueline; Roldán, Emilio; et al.; First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 21; 10-2025; 1-271422-0067CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/1422-0067/26/21/10622info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms262110622info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2026-03-31T15:24:38Zoai:ri.conicet.gov.ar:11336/282023instacron: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:34982026-03-31 15:24:38.576CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera
title First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera
spellingShingle First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera
Agüero, Facundo Ariel
glyceraldehyde 3 phosphate dehydrogenase
in silico analysis
Echinococcus granulosus
molecular dynamics simulation
title_short First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera
title_full First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera
title_fullStr First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera
title_full_unstemmed First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera
title_sort First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera
dc.creator.none.fl_str_mv Agüero, Facundo Ariel
Maglioco, Andrea Florencia
Valacco, Maria Pia
Juarez Valdez, Alejandra Yaqueline
Roldán, Emilio
Paulino, Margot
Fuchs, Alicia Graciela
author Agüero, Facundo Ariel
author_facet Agüero, Facundo Ariel
Maglioco, Andrea Florencia
Valacco, Maria Pia
Juarez Valdez, Alejandra Yaqueline
Roldán, Emilio
Paulino, Margot
Fuchs, Alicia Graciela
author_role author
author2 Maglioco, Andrea Florencia
Valacco, Maria Pia
Juarez Valdez, Alejandra Yaqueline
Roldán, Emilio
Paulino, Margot
Fuchs, Alicia Graciela
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv glyceraldehyde 3 phosphate dehydrogenase
in silico analysis
Echinococcus granulosus
molecular dynamics simulation
topic glyceraldehyde 3 phosphate dehydrogenase
in silico analysis
Echinococcus granulosus
molecular dynamics simulation
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.2
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Cystic echinococcosis (CE) is an endemic zoonotic disease caused by Echinococcus granulosus, which forms cysts in ungulates’ intermediate hosts. Humans are accidental hosts, and CE affects more than one million people worldwide. Imaging remains the diagnostic gold standard, outperforming serological methods. This study presents an in silico analysis of two glyceraldehyde-3-phosphate dehydrogenase (GAPDH) isoenzymes from E. granulosus (EgGAPDH), isolated from a parasite cell line (EGPE). EgGAPDHs were recognized by sera from CE patients, identified through LC-MS/MS and PCR of metacestodes from cattle liver. One isoenzyme is intracellular (IC) (UniProt: W6UJ19), and the other is extracellular (EC) (UniProt: W6V1T8). GAPDH is involved in host–parasite interactions and metabolic processes. We characterized the physicochemical properties; linear epitopes (LEPs); and amino acid domains of EgGAPDH, its hosts, and other parasites. W6UJ19 emerged as the most promising isoenzyme as a marker of infection. Molecular dynamics simulations of isoenzymes, performed in the presence or absence of two bisphosphonates (BPs), revealed how drug binding alters conformational epitopes (CEPs) and suggested that W6UJ19 is more responsive to BP modulation. Binding affinity analysis using the MMPBSA method revealed that etidronate (EHDP) binds EgGAPDH with greater affinity than phosphate (Pi) and alendronate (AL), in the following order: EHDP > Pi > AL.
Fil: Agüero, Facundo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; Argentina
Fil: Maglioco, Andrea Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; Argentina
Fil: Valacco, Maria Pia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Juarez Valdez, Alejandra Yaqueline. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Roldán, Emilio. Universidad Abierta Interamericana; Argentina
Fil: Paulino, Margot. Universidad de la República; Uruguay
Fil: Fuchs, Alicia Graciela. Universidad Abierta Interamericana; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina
description Cystic echinococcosis (CE) is an endemic zoonotic disease caused by Echinococcus granulosus, which forms cysts in ungulates’ intermediate hosts. Humans are accidental hosts, and CE affects more than one million people worldwide. Imaging remains the diagnostic gold standard, outperforming serological methods. This study presents an in silico analysis of two glyceraldehyde-3-phosphate dehydrogenase (GAPDH) isoenzymes from E. granulosus (EgGAPDH), isolated from a parasite cell line (EGPE). EgGAPDHs were recognized by sera from CE patients, identified through LC-MS/MS and PCR of metacestodes from cattle liver. One isoenzyme is intracellular (IC) (UniProt: W6UJ19), and the other is extracellular (EC) (UniProt: W6V1T8). GAPDH is involved in host–parasite interactions and metabolic processes. We characterized the physicochemical properties; linear epitopes (LEPs); and amino acid domains of EgGAPDH, its hosts, and other parasites. W6UJ19 emerged as the most promising isoenzyme as a marker of infection. Molecular dynamics simulations of isoenzymes, performed in the presence or absence of two bisphosphonates (BPs), revealed how drug binding alters conformational epitopes (CEPs) and suggested that W6UJ19 is more responsive to BP modulation. Binding affinity analysis using the MMPBSA method revealed that etidronate (EHDP) binds EgGAPDH with greater affinity than phosphate (Pi) and alendronate (AL), in the following order: EHDP > Pi > AL.
publishDate 2025
dc.date.none.fl_str_mv 2025-10
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/11336/282023
Agüero, Facundo Ariel; Maglioco, Andrea Florencia; Valacco, Maria Pia; Juarez Valdez, Alejandra Yaqueline; Roldán, Emilio; et al.; First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 21; 10-2025; 1-27
1422-0067
CONICET Digital
CONICET
url http://hdl.handle.net/11336/282023
identifier_str_mv Agüero, Facundo Ariel; Maglioco, Andrea Florencia; Valacco, Maria Pia; Juarez Valdez, Alejandra Yaqueline; Roldán, Emilio; et al.; First In Silico Study of Two Echinococcus granulosus Glyceraldehyde-3-Phosphate Dehydrogenase Isoenzymes Recognized by Liver Cystic Echinococcosis Human Sera; Molecular Diversity Preservation International; International Journal of Molecular Sciences; 26; 21; 10-2025; 1-27
1422-0067
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.mdpi.com/1422-0067/26/21/10622
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms262110622
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 Molecular Diversity Preservation International
publisher.none.fl_str_mv Molecular Diversity Preservation International
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_ 1861214727295729664
score 12.822162

Publicaciones similares