The human olfactory receptor 17-40: Requisites for fitting into the binding pocket

To gain structural insight on the interactions between odorants and the human olfactory receptor, we did homology modelling of the receptor structure, followed by molecular docking simulation with ligands. Molecular dynamics simulation on the structures resulting from docking served to estimate the binding free energy of the various odorant families. A correlation with the odorous properties of the ligands is proposed. We also investigated which residues were involved in the binding of a set of properly synthesised ligands and which were required for fitting inside the binding pocket. Olfactive stimulation of the olfactory receptor with odorous molecules was also investigated, using calcium imaging or electrophysiological recordings.

[1]  Chiquito J Crasto,et al.  Structural activation pathways from dynamic olfactory receptor-odorant interactions. , 2005, Chemical senses.

[2]  L. Buck,et al.  The human olfactory receptor gene family. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[3]  G. Gisselmann,et al.  Cloning, functional expression and characterization of a human olfactory receptor. , 1999, Cellular and molecular biology.

[4]  H. Matsunami.  Functional expression of Mammalian odorant receptors. , 2005, Chemical senses.

[5]  M. Burghammer,et al.  Crystal structure of the human β2 adrenergic G-protein-coupled receptor , 2007, Nature.

[6]  H. Sakano,et al.  Functional identification and reconstitution of an odorant receptor in single olfactory neurons. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  K. Lundstrom,et al.  Expression and intracellular localisation of odorant receptors in mammalian cell lines using Semliki Forest virus vectors. , 1999, Journal of receptor and signal transduction research.

[8]  David S. Goodsell,et al.  Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function , 1998 .

[9]  C. Wawrzeńczyk,et al.  Odoriferous derivatives of (E)-3,7,7-trimethyl-4-octen-1-ol and its 7-sila analogue , 1995 .

[10]  M. Afshar,et al.  Towards structural models of molecular recognition in olfactory receptors. , 1998, Biochimie.

[11]  J. Massagué.  TGF-beta signal transduction. , 1998, Annual review of biochemistry.

[12]  P Duchamp-Viret,et al.  Peripheral Odor Coding in the Rat and Frog: Quality and Intensity Specification , 2000, The Journal of Neuroscience.

[13]  N. Guex,et al.  SWISS‐MODEL and the Swiss‐Pdb Viewer: An environment for comparative protein modeling , 1997, Electrophoresis.

[14]  H. Hatt,et al.  Prediction of perception: probing the hOR17-4 olfactory receptor model with silicon analogues of bourgeonal and lilial. , 2007, Angewandte Chemie.

[15]  Linda B Buck,et al.  Unraveling the sense of smell (Nobel lecture). , 2005, Angewandte Chemie.

[16]  T. Straatsma,et al.  Free energy of ionic hydration: Analysis of a thermodynamic integration technique to evaluate free energy differences by molecular dynamics simulations , 1988 .

[17]  D. Eisenberg,et al.  Analysis of membrane and surface protein sequences with the hydrophobic moment plot. , 1984, Journal of molecular biology.

[18]  Hanns Hatt,et al.  Specificity and Sensitivity of a Human Olfactory Receptor Functionally Expressed in Human Embryonic Kidney 293 Cells andXenopus Laevis Oocytes , 1999, The Journal of Neuroscience.

[19]  H. Breer,et al.  Responsiveness of olfactory neurons to distinct aliphatic aldehydes. , 2000, The Journal of experimental biology.

[20]  R. Axel,et al.  A novel multigene family may encode odorant receptors: A molecular basis for odor recognition , 1991, Cell.

[21]  Nagarajan Vaidehi,et al.  Making sense of olfaction through predictions of the 3-D structure and function of olfactory receptors. , 2004, Chemical senses.

[22]  K. Mikoshiba,et al.  Functional expression of a mammalian odorant receptor. , 1998, Science.

[23]  D. Lancet,et al.  Sequence analysis in the olfactory receptor gene cluster on human chromosome 17: recombinatorial events affecting receptor diversity. , 1996, Genomics.

[24]  R. Araneda,et al.  The molecular receptive range of an odorant receptor , 2000, Nature Neuroscience.

[25]  Marie-Annick Persuy,et al.  Ligand-specific dose-response of heterologously expressed olfactory receptors. , 2003, European journal of biochemistry.

[26]  M. S. Singer,et al.  Analysis of the molecular basis for octanal interactions in the expressed rat 17 olfactory receptor. , 2000, Chemical senses.

[27]  L. Buck,et al.  The mouse olfactory receptor gene family , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Synthesis and odour properties of floral smelling compounds , 1996, International journal of cosmetic science.

[29]  L. Buck,et al.  Combinatorial Receptor Codes for Odors , 1999, Cell.

[30]  Nagarajan Vaidehi,et al.  Predicted 3-D structures for mouse I7 and rat I7 olfactory receptors and comparison of predicted odor recognition profiles with experiment. , 2004, Chemical senses.

[31]  Berk Hess,et al.  GROMACS 3.0: a package for molecular simulation and trajectory analysis , 2001 .

[32]  Manfred Burghammer,et al.  Structure of bovine rhodopsin in a trigonal crystal form. , 2003, Journal of molecular biology.

[33]  D. van der Spoel,et al.  Efficient docking of peptides to proteins without prior knowledge of the binding site , 2002, Protein science : a publication of the Protein Society.

[34]  Horst Vogel,et al.  Characterization of an extended receptive ligand repertoire of the human olfactory receptor OR17‐40 comprising structurally related compounds , 2006, Journal of neurochemistry.

[35]  A. Malhotra,et al.  The Molecular Basis for Ligand Specificity in a Mouse Olfactory Receptor , 2007, Journal of Biological Chemistry.

[36]  A. Gimelbrant,et al.  Olfactory Receptor Trafficking Involves Conserved Regulatory Steps* , 2001, The Journal of Biological Chemistry.