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

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 car boxylesterase B (CestB), was previously described as inducible in adult parasites under anthelmintic treatment an...

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Autores principales: Miranda-Miranda, Estefan, Scarcella, Silvana, Reynaud, Enrique, Narváez-Padilla, Verónica, Neira, Gisela, Mera y Sierra, Roberto, Aguilar-Díaz, Hugo, Cossio-Bayugar, Raquel
Formato: Artículo Científico
Lenguaje:Inglés
Publicado: Comite editorial GENES 2022
Materias:
SNTP
Carboxylesterase
Amino acid substitution
Fasciola hepatica
Anthelmintic resistance
Bioinformatics
Acceso en línea:https://repositorio.umaza.edu.ar/handle/00261/3093
Aporte de:
UMAZA Digital (Universidad MAZA - Mendoza) de Universidad Juan Agustín MAZA
id I56-R162-00261-3093
record_format dspace
spelling I56-R162-00261-30932024-10-04T12:48:40Z A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B Miranda-Miranda, Estefan Scarcella, Silvana Reynaud, Enrique Narváez-Padilla, Verónica Neira, Gisela Mera y Sierra, Roberto Aguilar-Díaz, Hugo Cossio-Bayugar, Raquel SNTP Carboxylesterase Amino acid substitution Fasciola hepatica Anthelmintic resistance Bioinformatics 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 car boxylesterase 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. 2022-11-09T14:39:17Z 2022-11-09T14:39:17Z 2022-10-19 Artículo Científico Miranda-Miranda, E., Scarcella, S., Reynaud, E., Narváez-Padilla, V., Neira, G., Mera y Sierra, R., Aguilar-Díaz, H. & Cossio-Bayugar, R. (2022). A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B. Revista Genes 2022, 13 (10): 1899. https://doi.org/10.3390/genes13101899. 2673-9976 https://repositorio.umaza.edu.ar/handle/00261/3093 eng info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4425/13/10/1899 application/pdf Comite editorial GENES 13,1899
institution Universidad Juan Agustín MAZA
institution_str I-56
repository_str R-162
collection UMAZA Digital (Universidad MAZA - Mendoza)
language Inglés
orig_language_str_mv eng
topic SNTP
Carboxylesterase
Amino acid substitution
Fasciola hepatica
Anthelmintic resistance
Bioinformatics
spellingShingle SNTP
Carboxylesterase
Amino acid substitution
Fasciola hepatica
Anthelmintic resistance
Bioinformatics
Miranda-Miranda, Estefan
Scarcella, Silvana
Reynaud, Enrique
Narváez-Padilla, Verónica
Neira, Gisela
Mera y Sierra, Roberto
Aguilar-Díaz, Hugo
Cossio-Bayugar, Raquel
A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
topic_facet SNTP
Carboxylesterase
Amino acid substitution
Fasciola hepatica
Anthelmintic resistance
Bioinformatics
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 car boxylesterase 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.
format Artículo Científico
author Miranda-Miranda, Estefan
Scarcella, Silvana
Reynaud, Enrique
Narváez-Padilla, Verónica
Neira, Gisela
Mera y Sierra, Roberto
Aguilar-Díaz, Hugo
Cossio-Bayugar, Raquel
author_facet Miranda-Miranda, Estefan
Scarcella, Silvana
Reynaud, Enrique
Narváez-Padilla, Verónica
Neira, Gisela
Mera y Sierra, Roberto
Aguilar-Díaz, Hugo
Cossio-Bayugar, Raquel
author_sort Miranda-Miranda, Estefan
title A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
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 single nucleotide polymorphism translates into a radical amino acid substitution at the ligand-binding site in fasciola hepatica carboxylesterase b
publisher Comite editorial GENES
publishDate 2022
url https://repositorio.umaza.edu.ar/handle/00261/3093
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