Decoding Molecular Mechanism Underlying Human Olfactory Receptor OR8D1 Activation by Sotolone Enantiomers.
J Agric Food Chem
; 72(10): 5403-5415, 2024 Mar 13.
Article
en En
| MEDLINE
| ID: mdl-38386648
ABSTRACT
Sotolone, a chiral compound, plays an important role in the food industry. Herein, (R)-/(S)-sotolone were separated to determine their odor characteristics and thresholds in air (R-form smoky, burned, herb, and green aroma, 0.0514 µg/m3; S-form sweet, milk, acid, and nutty aroma, 0.0048 µg/m3). OR8D1 responses to (R)-/(S)-sotolone were detected in a HEK293 cell-based luminescence assay. (S)-Sotolone was a more potent agonist than (R)-sotolone (EC50 values of 84.98 ± 1.05 and 167.20 ± 0.25 µmol/L, respectively). Molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area analyses confirmed that the combination of (S)-sotolone and OR8D1 was more stable than that of (R)-sotolone. Odorant docking, multiple sequence alignments, site-directed mutagenesis, and functional studies with recombinant odorant receptors (ORs) in a cell-based luminescence assay identified 11 amino-acid residues that influence the enantioselectivity of OR8D1 toward sotolone significantly and that N2065.46 was indispensable to the activation of OR8D1 by (S)-sotolone.
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Base de datos:
MEDLINE
Asunto principal:
Receptores Odorantes
Idioma:
En
Revista:
J Agric Food Chem
/
J. agric. Food chem
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Journal of agricultural and food chemistry
Año:
2024
Tipo del documento:
Article