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

Autor: Estefan Miranda-Miranda, Silvana Scarcella, Enrique Reynaud, Verónica Narváez-Padilla, Gisela Neira, Roberto Mera-y-Sierra, Hugo Aguilar-Díaz, Raquel Cossio-Bayugar
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Genes; Volume 13; Issue 10; Pages: 1899
13,1899
UMaza Digital
Universidad Maza
instacron:UMAZA
ISSN: 2073-4425
DOI: 10.3390/genes13101899
Popis: Fil: Miranda-Miranda, Estefan. Instituto Nacional de Investigaciones Forestales Agrícolas y Pecuarias (INIFAP). Centro Nacional de Investigaciones Disciplinarias en Salud Animal e Inocuidad. Departamento de Artropodología. Morelos. México. Fil: Scarcella, Silvana. Laboratorio de Biología Celular y Molecular. Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET. UNCPBA. Tandil. República Argentina. Fil: Reynaud, Enrique. Universidad Nacional Autónoma de México. Instituto de Biotecnología. Departamento de Genética del Desarrollo y Fisiología Molecular. Morelos. México. Fil: Narváez-Padilla, Verónica. Universidad Autónoma del Estado de Morelos. Centro de Investigación en Dinámica Celular. Morelos. México. Fil: Neira, Gisela. Universidad Juan Agustín Maza. Centro de Investigación en Parasitología Regional (CIPAR). Mendoza. República Argentina. Fil: Mera y Sierra, Roberto. Universidad Juan Agustín Maza. Centro de Investigación en Parasitología Regional (CIPAR). Mendoza. República Argentina. Fil: Aguilar-Díaz, Hugo. Instituto Nacional de Investigaciones Forestales Agrícolas y Pecuarias (INIFAP). Centro Nacional de Investigaciones Disciplinarias en Salud Animal e Inocuidad. Departamento de Artropodología. Morelos. México. Fil: Cossio-Bayugar, Raquel. Instituto Nacional de Investigaciones Forestales Agrícolas y Pecuarias (INIFAP). Centro Nacional de Investigaciones Disciplinarias en Salud Animal e Inocuidad. Departamento de Artropodología. Morelos. México. 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.
Databáze: OpenAIRE
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