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

dc.creatorMiranda-Miranda, Estefan
dc.creatorScarcella, Silvana
dc.creatorReynaud, Enrique
dc.creatorNarváez-Padilla, Verónica
dc.creatorNeira, Gisela
dc.creatorMera y Sierra, Roberto
dc.creatorAguilar-Díaz, Hugo
dc.creatorCossio-Bayugar, Raquel
dc.date2022-11-09T14:39:17Z
dc.date2022-11-09T14:39:17Z
dc.date2022-10-19
dc.identifierMiranda-Miranda, E., Scarcella, S., Reynaud, E., Narváez-Padilla, V., Neira, G., Mera y Sierra, R., Aguilar-Díaz, H. y 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.
dc.identifier2673-9976
dc.identifierhttp://repositorio.umaza.edu.ar/xmlui/handle/00261/3093
dc.identifierhttps://www.mdpi.com/2073-4425/13/10/1899
dc.descriptionFasciola 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherComite editorial GENES
dc.source13,1899
dc.subjectSNTP
dc.subjectCarboxylesterase
dc.subjectAmino acid substitution
dc.subjectFasciola hepatica
dc.subjectAnthelmintic resistance
dc.subjectBioinformatics
dc.titleA Single Nucleotide Polymorphism Translates into a Radical Amino Acid Substitution at the Ligand-Binding Site in Fasciola hepatica Carboxylesterase B
dc.typeArtículo Científico


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