Chem. Senses 25: 155-165,
2000
© Oxford University Press 2000
Analysis of the Molecular Basis for Octanal Interactions in the Expressed Rat I7 Olfactory Receptor
Section of Neurobiology and Center for Medical Informatics, Yale University School of Medicine, 236 FMB, 333 Cedar Street, New Haven, CT 06520, USA
Correspondence to be sent to: Michael Singer, Section of Neurobiology, Yale University School of Medicine, 236 FMB, 333 Cedar Street, New Haven, CT 06520, USA. e-mail: mike{at}habibi.med.yale.edu
Expression studies have shown that the rat I7 olfactory receptor (OR-I7) responds preferentially to the aldehyde n-octanal. We wished to predict which residues in OR-I7 bind octanal and how the biophysical properties of these residues determine the receptor’s odor selectivity. Building on our previous work on aldehyde interactions in olfactory receptors, we constructed a molecular model of OR-I7 based on the 7.5 Å resolution three-dimensional map of rhodopsin. Octanal was automatically docked in the model. The results predicted an odor-binding pocket ~10 Å from the extracellular surface, in a location similar to the epinephrine-binding pocket of the beta-adrenergic receptor and the odor-binding pocket of a previous olfactory receptor model. A lysine on TM4 and an aspartate on TM5 interacted with the aldehyde moiety of octanal. Hydrophobic residues formed Van der Waals contacts with the hydrocarbon portion of octanal. We docked related odor compounds and found that the predicted affinities compared favorably with experimental results. We also tested a number of amino acid substitutions in order to predict their effects on octanal affinity and provide leads for future experimental work.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Reisert and D. Restrepo Molecular Tuning of Odorant Receptors and Its Implication for Odor Signal Processing Chem Senses, September 1, 2009; 34(7): 535 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Abaffy, A. Malhotra, and C. W. Luetje The Molecular Basis for Ligand Specificity in a Mouse Olfactory Receptor: A NETWORK OF FUNCTIONALLY IMPORTANT RESIDUES J. Biol. Chem., January 12, 2007; 282(2): 1216 - 1224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Mori, Y. K. Takahashi, K. M. Igarashi, and M. Yamaguchi Maps of Odorant Molecular Features in the Mammalian Olfactory Bulb Physiol Rev, April 1, 2006; 86(2): 409 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Lai, M. S. Singer, and C. J. Crasto Structural Activation Pathways from Dynamic Olfactory Receptor-Odorant Interactions Chem Senses, November 1, 2005; 30(9): 781 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Katada, T. Hirokawa, Y. Oka, M. Suwa, and K. Touhara Structural Basis for a Broad But Selective Ligand Spectrum of a Mouse Olfactory Receptor: Mapping the Odorant-Binding Site J. Neurosci., February 16, 2005; 25(7): 1806 - 1815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Shepherd Outline of a Theory of Olfactory Processing and its Relevance to Humans Chem Senses, January 1, 2005; 30(suppl_1): i3 - i5. [Full Text] [PDF]
|
|
|
|
|
|
S. E. Hall, W. B. Floriano, N. Vaidehi, and W. A. Goddard III Predicted 3-D Structures for Mouse I7 and Rat I7 Olfactory Receptors and Comparison of Predicted Odor Recognition Profiles with Experiment Chem Senses, September 1, 2004; 29(7): 595 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. B. Floriano, N. Vaidehi, and W. A. Goddard III Making Sense of Olfaction through Predictions of the 3-D Structure and Function of Olfactory Receptors Chem Senses, May 1, 2004; 29(4): 269 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. D. Emes, S. A. Beatson, C. P. Ponting, and L. Goodstadt Evolution and Comparative Genomics of Odorant- and Pheromone-Associated Genes in Rodents Genome Res., April 1, 2004; 14(4): 591 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Gaillard, S. Rouquier, A. Chavanieu, P. Mollard, and D. Giorgi Amino-acid changes acquired during evolution by olfactory receptor 912-93 modify the specificity of odorant recognition Hum. Mol. Genet., April 1, 2004; 13(7): 771 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Reisenman, T. A. Christensen, W. Francke, and J. G. Hildebrand Enantioselectivity of Projection Neurons Innervating Identified Olfactory Glomeruli J. Neurosci., March 17, 2004; 24(11): 2602 - 2611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Xu, N. Liu, I. Kida, D. L. Rothman, F. Hyder, and G. M. Shepherd Odor maps of aldehydes and esters revealed by functional MRI in the glomerular layer of the mouse olfactory bulb PNAS, September 16, 2003; 100(19): 11029 - 11034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hamana, J. Hirono, M. Kizumi, and T. Sato Sensitivity-dependent Hierarchical Receptor Codes for Odors Chem Senses, February 1, 2003; 28(2): 87 - 104. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Crasto, L. Marenco, P. Miller, and G. Shepherd Olfactory Receptor Database: a metadata-driven automated population from sources of gene and protein sequences Nucleic Acids Res., January 1, 2002; 30(1): 354 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. L. Miller, P. Nadkarni, M. Singer, L. Marenco, M. Hines, and G. Shepherd Integration of Multidisciplinary Sensory Data:: A Pilot Model of the Human Brain Project Approach J. Am. Med. Inform. Assoc., January 1, 2001; 8(1): 34 - 48. [Abstract] [Full Text]
|
|
|
|
|
|
M. Ma and G. M. Shepherd Functional mosaic organization of mouse olfactory receptor neurons PNAS, October 23, 2000; (2000) 220301797. [Abstract] [Full Text]
|
|
|
|
|
|
M. Ma and G. M. Shepherd Functional mosaic organization of mouse olfactory receptor neurons PNAS, November 7, 2000; 97(23): 12869 - 12874. [Abstract] [Full Text] [PDF]
|
|