Linked Life Data

15467253

Source:http://linkedlifedata.com/resource/pubmed/id/15467253

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-10-6
pubmed:abstractText
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 EC50 values ranging from a few microM to several hundred microM. 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 EC50 value of eugenol in Ca2+ 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.
pubmed:language
jpn
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0015-5691
pubmed:author
pubmed:issnType
Print
pubmed:volume
124
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
201-9
pubmed:dateRevised
2011-7-27
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
[A molecular basis for odorant recognition: olfactory receptor pharmacology].
pubmed:affiliation
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562, Japan.
pubmed:publicationType
Journal Article, English Abstract, Review