A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B

Autores
Miranda-Miranda, Estefan; Scarcella, Silvana Andrea; Reynaud, Enrique; Narváez Padilla, Verónica; Neira, Gisela Natalia; Mera y Sierra, Roberto; Aguilar Díaz, Hugo; Cossio Bayugar, Raquel
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fasciola hepatica anthelmintic resistance may be associated with the catalytic activity of xenobiotic metabolizing enzymes. The gene expression of one of these enzymes, identified as carboxylesterase B (CestB), was previously described as inducible in adult parasites under anthelmintic treatment and exhibited a single nucleotide polymorphism at position 643 that translates into a radical amino acid substitution at position 215 from Glutamic acid to Lysine. Alphafold 3D models of both allelic sequences exhibited a significant affinity pocket rearrangement and different ligand-docking modeling results. Further bioinformatics analysis confirmed that the radical amino acid substitution is located at the ligand affinity site of the enzyme, affecting its affinity to serine hydrolase inhibitors and preferences for ester ligands. A field genotyping survey from parasite samples obtained from two developmental stages isolated from different host species from Argentina and Mexico exhibited a 37% allele distribution for 215E and a 29% allele distribution for 215K as well as a 34% E/K heterozygous distribution. No linkage to host species or geographic origin was found in any of the allele variants.
Fil: Miranda-Miranda, Estefan. Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias; México
Fil: Scarcella, Silvana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Reynaud, Enrique. Universidad Nacional Autónoma de México; México
Fil: Narváez Padilla, Verónica. Universidad Autónoma del Estado de Morelos; México
Fil: Neira, Gisela Natalia. Universidad "Juan Agustín Maza". Facultad de Ciencias Veterinarias y Ambientales. Centro de Investigación en Parasitología Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Mera y Sierra, Roberto. Universidad "Juan Agustín Maza". Facultad de Ciencias Veterinarias y Ambientales. Centro de Investigación en Parasitología Regional; Argentina
Fil: Aguilar Díaz, Hugo. Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias; México
Fil: Cossio Bayugar, Raquel. Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias; México
Materia
AMINO ACID SUBSTITUTION
ANTHELMINTIC RESISTANCE
BIOINFORMATICS
CARBOXYLESTERASE
FASCIOLA HEPATICA
SNTP
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/197834
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/197834
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase BMiranda-Miranda, EstefanScarcella, Silvana AndreaReynaud, EnriqueNarváez Padilla, VerónicaNeira, Gisela NataliaMera y Sierra, RobertoAguilar Díaz, HugoCossio Bayugar, RaquelAMINO ACID SUBSTITUTIONANTHELMINTIC RESISTANCEBIOINFORMATICSCARBOXYLESTERASEFASCIOLA HEPATICASNTPhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Fasciola hepatica anthelmintic resistance may be associated with the catalytic activity of xenobiotic metabolizing enzymes. The gene expression of one of these enzymes, identified as carboxylesterase B (CestB), was previously described as inducible in adult parasites under anthelmintic treatment and exhibited a single nucleotide polymorphism at position 643 that translates into a radical amino acid substitution at position 215 from Glutamic acid to Lysine. Alphafold 3D models of both allelic sequences exhibited a significant affinity pocket rearrangement and different ligand-docking modeling results. Further bioinformatics analysis confirmed that the radical amino acid substitution is located at the ligand affinity site of the enzyme, affecting its affinity to serine hydrolase inhibitors and preferences for ester ligands. A field genotyping survey from parasite samples obtained from two developmental stages isolated from different host species from Argentina and Mexico exhibited a 37% allele distribution for 215E and a 29% allele distribution for 215K as well as a 34% E/K heterozygous distribution. No linkage to host species or geographic origin was found in any of the allele variants.Fil: Miranda-Miranda, Estefan. Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias; MéxicoFil: Scarcella, Silvana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Reynaud, Enrique. Universidad Nacional Autónoma de México; MéxicoFil: Narváez Padilla, Verónica. Universidad Autónoma del Estado de Morelos; MéxicoFil: Neira, Gisela Natalia. Universidad "Juan Agustín Maza". Facultad de Ciencias Veterinarias y Ambientales. Centro de Investigación en Parasitología Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; ArgentinaFil: Mera y Sierra, Roberto. Universidad "Juan Agustín Maza". Facultad de Ciencias Veterinarias y Ambientales. Centro de Investigación en Parasitología Regional; ArgentinaFil: Aguilar Díaz, Hugo. Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias; MéxicoFil: Cossio Bayugar, Raquel. Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias; MéxicoMDPI2022-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/197834Miranda-Miranda, Estefan; Scarcella, Silvana Andrea; Reynaud, Enrique; Narváez Padilla, Verónica; Neira, Gisela Natalia; et al.; A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B; MDPI; Genes; 13; 10; 10-2022; 1-112073-4425CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3390/genes13101899info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:10:14Zoai:ri.conicet.gov.ar:11336/197834instacron: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:34982025-10-22 11:10:14.485CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
title A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
spellingShingle A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
Miranda-Miranda, Estefan
AMINO ACID SUBSTITUTION
ANTHELMINTIC RESISTANCE
BIOINFORMATICS
CARBOXYLESTERASE
FASCIOLA HEPATICA
SNTP
title_short A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
title_full A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
title_fullStr A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
title_full_unstemmed A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
title_sort A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
dc.creator.none.fl_str_mv Miranda-Miranda, Estefan
Scarcella, Silvana Andrea
Reynaud, Enrique
Narváez Padilla, Verónica
Neira, Gisela Natalia
Mera y Sierra, Roberto
Aguilar Díaz, Hugo
Cossio Bayugar, Raquel
author Miranda-Miranda, Estefan
author_facet Miranda-Miranda, Estefan
Scarcella, Silvana Andrea
Reynaud, Enrique
Narváez Padilla, Verónica
Neira, Gisela Natalia
Mera y Sierra, Roberto
Aguilar Díaz, Hugo
Cossio Bayugar, Raquel
author_role author
author2 Scarcella, Silvana Andrea
Reynaud, Enrique
Narváez Padilla, Verónica
Neira, Gisela Natalia
Mera y Sierra, Roberto
Aguilar Díaz, Hugo
Cossio Bayugar, Raquel
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AMINO ACID SUBSTITUTION
ANTHELMINTIC RESISTANCE
BIOINFORMATICS
CARBOXYLESTERASE
FASCIOLA HEPATICA
SNTP
topic AMINO ACID SUBSTITUTION
ANTHELMINTIC RESISTANCE
BIOINFORMATICS
CARBOXYLESTERASE
FASCIOLA HEPATICA
SNTP
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Fasciola hepatica anthelmintic resistance may be associated with the catalytic activity of xenobiotic metabolizing enzymes. The gene expression of one of these enzymes, identified as carboxylesterase B (CestB), was previously described as inducible in adult parasites under anthelmintic treatment and exhibited a single nucleotide polymorphism at position 643 that translates into a radical amino acid substitution at position 215 from Glutamic acid to Lysine. Alphafold 3D models of both allelic sequences exhibited a significant affinity pocket rearrangement and different ligand-docking modeling results. Further bioinformatics analysis confirmed that the radical amino acid substitution is located at the ligand affinity site of the enzyme, affecting its affinity to serine hydrolase inhibitors and preferences for ester ligands. A field genotyping survey from parasite samples obtained from two developmental stages isolated from different host species from Argentina and Mexico exhibited a 37% allele distribution for 215E and a 29% allele distribution for 215K as well as a 34% E/K heterozygous distribution. No linkage to host species or geographic origin was found in any of the allele variants.
Fil: Miranda-Miranda, Estefan. Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias; México
Fil: Scarcella, Silvana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Reynaud, Enrique. Universidad Nacional Autónoma de México; México
Fil: Narváez Padilla, Verónica. Universidad Autónoma del Estado de Morelos; México
Fil: Neira, Gisela Natalia. Universidad "Juan Agustín Maza". Facultad de Ciencias Veterinarias y Ambientales. Centro de Investigación en Parasitología Regional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina
Fil: Mera y Sierra, Roberto. Universidad "Juan Agustín Maza". Facultad de Ciencias Veterinarias y Ambientales. Centro de Investigación en Parasitología Regional; Argentina
Fil: Aguilar Díaz, Hugo. Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias; México
Fil: Cossio Bayugar, Raquel. Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias; México
description Fasciola hepatica anthelmintic resistance may be associated with the catalytic activity of xenobiotic metabolizing enzymes. The gene expression of one of these enzymes, identified as carboxylesterase B (CestB), was previously described as inducible in adult parasites under anthelmintic treatment and exhibited a single nucleotide polymorphism at position 643 that translates into a radical amino acid substitution at position 215 from Glutamic acid to Lysine. Alphafold 3D models of both allelic sequences exhibited a significant affinity pocket rearrangement and different ligand-docking modeling results. Further bioinformatics analysis confirmed that the radical amino acid substitution is located at the ligand affinity site of the enzyme, affecting its affinity to serine hydrolase inhibitors and preferences for ester ligands. A field genotyping survey from parasite samples obtained from two developmental stages isolated from different host species from Argentina and Mexico exhibited a 37% allele distribution for 215E and a 29% allele distribution for 215K as well as a 34% E/K heterozygous distribution. No linkage to host species or geographic origin was found in any of the allele variants.
publishDate 2022
dc.date.none.fl_str_mv 2022-10
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/11336/197834
Miranda-Miranda, Estefan; Scarcella, Silvana Andrea; Reynaud, Enrique; Narváez Padilla, Verónica; Neira, Gisela Natalia; et al.; A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B; MDPI; Genes; 13; 10; 10-2022; 1-11
2073-4425
CONICET Digital
CONICET
url http://hdl.handle.net/11336/197834
identifier_str_mv Miranda-Miranda, Estefan; Scarcella, Silvana Andrea; Reynaud, Enrique; Narváez Padilla, Verónica; Neira, Gisela Natalia; et al.; A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B; MDPI; Genes; 13; 10; 10-2022; 1-11
2073-4425
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3390/genes13101899
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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 12.982451

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