A Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
Por:
Miranda-Miranda, Estefan, Scarcella, Silvana, Reynaud, Enrique, Narvaez-Padilla, Veronica, Neira, Gisela, Mera-Y-Sierra, Roberto, Aguilar-Diaz, Hugo, Cossio-Bayugar, Raquel
Publicada:
1 oct 2022
Resumen:
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.
Filiaciones:
Miranda-Miranda, Estefan:
Departamento de Artropodología, Centro Nacional de Investigaciones Disciplinarias en Salud Animal e Inocuidad, Instituto Nacional de Investigaciones Forestales Agrícolas y Pecuarias (INIFAP), Boulevard Cuauhnahuac No. 8534, Morelos, Jiutepec, 62574, Mexico
Scarcella, Silvana:
Laboratorio de Biología Celular y Molecular, Centro de Investigación Veterinaria de Tandil (CIVETAN), CONICET, UNCPBA, Tandil, 7000, Argentina
Reynaud, Enrique:
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Campus Cuernavaca, Avenida Universidad, 2001, Apartado Postal 510–3, Morelos, Cuernavaca, 62210, Mexico
Narvaez-Padilla, Veronica:
Centro de Investigación en Dinámica Celular de la Universidad Autónoma del Estado de Morelos, Campus Cuernavaca Morelos México, Av. Universidad 1001, Chamilpa, Morelos, Cuernavaca, 62210, Mexico
Neira, Gisela:
Centro de Investigación en Parasitología Regional (CIPAR), Universidad J.A. Maza, Guaymallen, 5519, Argentina
Mera-Y-Sierra, Roberto:
Centro de Investigación en Parasitología Regional (CIPAR), Universidad J.A. Maza, Guaymallen, 5519, Argentina
Aguilar-Diaz, Hugo:
Departamento de Artropodología, Centro Nacional de Investigaciones Disciplinarias en Salud Animal e Inocuidad, Instituto Nacional de Investigaciones Forestales Agrícolas y Pecuarias (INIFAP), Boulevard Cuauhnahuac No. 8534, Morelos, Jiutepec, 62574, Mexico
Cossio-Bayugar, Raquel:
Departamento de Artropodología, Centro Nacional de Investigaciones Disciplinarias en Salud Animal e Inocuidad, Instituto Nacional de Investigaciones Forestales Agrícolas y Pecuarias (INIFAP), Boulevard Cuauhnahuac No. 8534, Morelos, Jiutepec, 62574, Mexico
gold, Green Published, Gold, Green
|