The G protein (Golf and/or Gs)[10] in turn activates the lyase - adenylate cyclase - which converts ATP into cyclic AMP (cAMP).

The primary sequences of thousands of olfactory receptors are known from the genomes of more than a dozen organisms: they are seven-helix transmembrane proteins, but there are very few solved structures.

[12] Golebiowski, Ma and Matsunami showed that the mechanism of ligand recognition, although similar to other non-olfactory class A GPCRs, involves residues specific to olfactory receptors, notably in the sixth helix.

[13] There is a highly conserved sequence in roughly three quarters of all ORs that is a tripodal metal ion binding site,[14] and Suslick has proposed that the ORs are in fact metalloproteins (mostly likely with zinc, copper and possibly manganese ions) that serve as a Lewis acid site for binding of many odorant molecules.

Crabtree, in 1978, had previously suggested that Cu(I) is "the most likely candidate for a metallo-receptor site in olfaction" for strong-smelling volatiles which are also good metal-coordinating ligands, such as thiols.

[15] Zhuang, Matsunami and Block, in 2012, confirmed the Crabtree/Suslick proposal for the specific case of a mouse OR, MOR244-3, showing that copper is essential for detection of certain thiols and other sulfur-containing compounds.

However, these authors also found that MOR244-3 lacks the specific metal ion binding site suggested by Suslick, instead showing a different motif in the EC2 domain.

[17] In a recent but highly controversial interpretation, it has also been speculated that olfactory receptors might really sense various vibrational energy-levels of a molecule rather than structural motifs via quantum coherence mechanisms.

Such isotope effects are exceedingly common, and so it is well known that deuterium substitution will indeed change the binding constants of molecules to protein receptors.

[20] It has been claimed that human olfactory receptors are capable of distinguishing between deuterated and undeuterated isotopomers of cyclopentadecanone by vibrational energy level sensing.

[21] However this claim has been challenged by another report that the human musk-recognizing receptor, OR5AN1 that robustly responds to cyclopentadecanone and muscone, fails to distinguish isotopomers of these compounds in vitro.

[28][29] Analogous to the immune system, the diversity that exists within the olfactory receptor family allows molecules that have never been encountered before to be characterized.

Using mathematical modeling and computer simulations, Tian et al proposed an evolutionarily optimized three-layer regulation mechanism, which includes zonal segregation, epigenetic barrier crossing coupled to a negative feedback loop and an enhancer competition step [32] .

Members belonging to the same subfamily of olfactory receptors (>60% sequence identity) are likely to recognize structurally similar odorant molecules.

[42] However, recent evidence has rendered the vision priority hypothesis obsolete, because it was based on misleading data and assumptions.

[47] In 2004 Linda B. Buck and Richard Axel won the Nobel Prize in Physiology or Medicine for their work[48] on olfactory receptors.