Structural determinants of a conserved enantiomer-selective carvone binding pocket in the human odorant receptor OR1A1.

Structural determinants of a conserved enantiomer-selective carvone binding pocket in the human odorant receptor OR1A1.
Cell Mol Life Sci. 2017 Jun 27;:
Authors: Geithe C, Protze J, Kreuchwig F, Krause G, Krautwurst D
Abstract
Chirality is a common phenomenon within odorants. Most pairs of enantiomers show only moderate differences in odor quality. One example for enantiomers that are easily discriminated by their odor quality is the carvones: humans significantly distinguish between the spearmint-like (R)-(-)-carvone and caraway-like (S)-(+)-carvone enantiomers. Moreover, for the (R)-(-)-carvone, an anosmia is observed in about 8% of the population, suggesting enantioselective odorant receptors (ORs). With only about 15% de-orphaned human ORs, the lack of OR crystal structures, and few comprehensive studies combining in silico and experimental approaches to elucidate structure-function relations of ORs, knowledge on cognate odorant/OR interactions is still sparse. An adjusted homology modeling approach considering OR-specific proline-caused conformations, odorant docking studies, single-nucleotide polymorphism (SNP) analysis, site-directed mutagenesis, and subsequent functional studies with recombinant ORs in a cell-based, real-time luminescence assay revealed 11 amino acid positions to constitute an enantioselective binding pocket necessary for a carvone function in human OR1A1 and murine Olfr43, respectively. Here, we identified e...

Source: Cellular and Molecular Life Sciences : CMLS - June 27, 2017 Category: Cytology Authors: Geithe C, Protze J, Kreuchwig F, Krause G, Krautwurst D Tags: Cell Mol Life Sci Source Type: research