A molecular basis for odorant recognition: Olfactory receptor pharmacology

Sayako Katada, Kazushige Touhara

Research output: Contribution to journalReview articlepeer-review

3 Citations (Scopus)

Abstract

Olfactory receptors (ORs) comprise the largest super-family of rhodopsin-like G-protein coupled receptors (GPCR) that involve the recognition and discrimination of thousands of odorants. We recently succeeded in functional reconstitution of mouse ORs in mammalian cell lines and provided molecular evidence that structurally-related ORs recognized overlapping sets of odorants with distinct ligand specificities. Here we show that mOR-EG, a mouse olfactory receptor that was isolated from a eugenol-responsive cell, recognizes 22 different odorants with EC50values ranging from a few μ M to several hundred μ M. We constructed a molecular model of mOR-EG using the recent atomic-level structure of bovine rhodopsin. Site-directed mutations were introduced in a potential ligand-binding pocket based on computational ligand-docking simulation. Mutations of some amino acid residues in TM3, TM5, and TM6 dramatically affected the EC50value of eugenol in Ca 2+ imaging. Finally, we succeeded in rational receptor design with predicted ligand specificity by introducing point mutations in the binding site, confirming the accuracy of the binding site mapping. The current studies also help understand mechanisms underlying molecular recognition by GPCRs, with implications for therapeutic application.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalFolia Pharmacologica Japonica
Volume124
Issue number4
DOIs
Publication statusPublished - 2004

All Science Journal Classification (ASJC) codes

  • Pharmacology

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