Structure of rat odorant-binding protein OBP1 at 1.6 angstrom resolution
The nasal mucosa is a specialist interfacial region sandwiched between the olfactory system and the gaseous chemical milieu. In mammals and insects, this region is rich in odorant-binding proteins that are thought to aid olfaction by assisting mass transfer of the many different organoleptic compounds that make up the olfactory landscape. However, in mammals at least, our grasp on the exact function of odorant-binding proteins is tentative and better insight into the role of these proteins is warranted, not least because of their apparent significance in the olfactory systems of insects. Here, the crystal structure of rat odorant-binding protein 1 is reported at 1.6 Å resolution. This prote…
Rapid odorant release in mammalian odour binding proteins facilitates their temporal coupling to odorant signals.
; We have measured the effect of rat odorant-binding protein 1 on the rates of ligand uptake and liquid-to-air transfer rates with a set of defined odorous compounds. Comparison of observed rate constants (k(obs)) with data simulated over a wide range of different kinetic and thermodynamic regimes shows that the data do not agree with the previously held view of a slow off-rate regime (k(off) <0.0004 s(-1)). We propose that a rapid koff would be a necessary requirement for such a system, since slow odorant-release rates would result in significant decorrelation between the olfactory world and odour perception. (c) 2010 Elsevier Ltd. All rights reserved.
Enthalpy/entropy compensation effects from cavity desolvation underpin broad ligand binding selectivity for rat odorant binding protein 3
Evolution has produced proteins with exquisite ligand binding specificity, and manipulating this effect has been the basis for much of modern rational drug design. However, there are general classes of proteins with broader ligand selectivity linked to function, the origin of which is poorly understood. The odorant binding proteins (OBPs) sequester volatile molecules for transportation to the olfactory receptors. Rat OBP3, which we characterize by X-ray crystallography and NMR, binds a homologous series of aliphatic gamma-lactones within its aromatic-rich hydrophobic pocket with remarkably little variation in affinity but extensive enthalpy/entropy compensation effects. We show that the bin…