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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/197834
Ver los metadatos del registro completo
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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 Técnicas2025-09-29T09:41:41Zoai: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:34982025-09-29 09:41:41.851CONICET 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 |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1844613314832760832 |
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13.070432 |