Ligand specificity of odorant receptors

@article{Khafizov2007LigandSO,
  title={Ligand specificity of odorant receptors},
  author={Kamil Khafizov and Claudio Anselmi and Anna Menini and Paolo Carloni},
  journal={Journal of Molecular Modeling},
  year={2007},
  volume={13},
  pages={401-409}
}
Odorant receptors belong to class A of the G protein-coupled receptors (GPCRs) and detect a large number of structurally diverse odorant molecules. A recent structural bioinformatic analysis suggests that structural features are conserved across class A of GPCRs in spite of their low sequence identity. Based on this work, we have aligned the sequences of 29 ORs for which ligand binding data are available. Recent site-directed mutagenesis experiments on one such receptor (MOR174-9) provide… 
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Olfactory receptors are sensitive to molecular volume of odorants
To study olfaction, first we should know which physical or chemical properties of odorant molecules determine the response of olfactory receptor neurons, and then we should study the effect of those
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References

SHOWING 1-10 OF 46 REFERENCES
Molecular modeling of ligand-receptor interactions in the OR5 olfactory receptor.
TLDR
A computer model of the OR5 olfactory receptor has been constructed and compared with other members of this superfamily, and docking of the odor molecule lyral is tested, pointing to specific ligand-binding residues on helices III through VII that form a binding pocket in the receptor.
Prediction of the odorant binding site of olfactory receptor proteins by human–mouse comparisons
TLDR
It is proposed that the identified sequence positions constitute the odorant binding site, supported by the observation that all but one of the predicted binding site residues correspond to ligand‐contact positions in other rhodopsin‐like GPCRs.
Structural Basis for a Broad But Selective Ligand Spectrum of a Mouse Olfactory Receptor: Mapping the Odorant-Binding Site
TLDR
The current study reveals the molecular environment of the odorant-binding site, and it further advances the understanding of GPCR pharmacology.
Molecular mechanisms underlying differential odor responses of a mouse olfactory receptor.
TLDR
The results provide a mechanistic model for olfactory transduction at the molecular level and show how the basic G protein-coupled receptor template is adapted for encoding the enormous odor space.
Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis.
TLDR
The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function, and two of these positions may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors.
Towards structural models of molecular recognition in olfactory receptors.
TLDR
This paper reviews recent developments in two areas of molecular modelling: methods for modelling the configuration of trans-membrane helices and methods for automatic docking of ligands into receptor structures and shows how a subset of these methods can be combined to construct a model of a rat odorant receptor interacting with lyral.
Genes and ligands for odorant, vomeronasal and taste receptors
  • P. Mombaerts
  • Chemistry, Biology
    Nature Reviews Neuroscience
  • 2004
TLDR
Targeted expression of the green fluorescent protein in chemosensory cells is a promising approach to achieve this objective of characterized receptor–ligand interactions.
RTP Family Members Induce Functional Expression of Mammalian Odorant Receptors
TLDR
It is shown that the transmembrane proteins RTP1 and RTP2 promote functional cell surface expression of ORs expressed in HEK293T cells, providing a platform for screening the chemical selectivity of the large OR family.
Identification of Ligands for Olfactory Receptors by Functional Expression of a Receptor Library
TLDR
The generation of an expression library containing a large and diverse repertoire of mouse olfactory receptor sequences in the transmembrane II-VII region is reported, and it is found that the mouse I7 receptor, unlike the rat I7 receptors, prefers heptanal instead of octanal, as a result of a single valine-to-isoleucine substitution.
Structural activation pathways from dynamic olfactory receptor-odorant interactions.
TLDR
This work has simulated an odor ligand's dynamic behavior in the binding region of an olfactory receptor (OR) and graphically traced the rotameric changes in key OR amino acid side chains during the transit, helping substantiate or refute previously held notions of amino acid contribution to ligand stability in thebinding pocket.
...
1
2
3
4
5
...