Molecular recognition in olfaction

Horsfield, Andrew P.; Haase, Andrea; Turin, Luca

doi:10.1080/23746149.2017.1378594

Cited by 19 publications

(32 citation statements)

References 113 publications

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“…In summary, in addi4on to the inelas4c tunneling mechanism proposed for olfac4on 5 , there may be other ways for a GPCR ligand to control electron flow. In the case of elas4c tunneling, control over the height of the tunnelling barrier could be effected merely by the ligand bearing a posi4ve charge to lower an empty orbital on the bridging molecule, which is of course the case for all biogenic amines and the vast majority of alkaloids (the term itself denotes a protonatable base).…”

Section: Figure 11mentioning

confidence: 99%

“…electron transfer from a donor via an odorant to an acceptor, enabled by excita4on of molecular vibra4ons in the odorant 1 . The physics behind this idea was shown to be sound [2][3][4][5][6] , and strong behavioural and perceptual evidence in its favour has come from experiments on insects and humans [7][8][9][10] . However, the idea currently remains controversial [11][12][13] , in part because vertebrate olfactory receptors are members of the G-protein-coupled receptor (GPCR) family: GPCRs are thought to work by a conven4onal lock and key mechanism 14,15 .…”

Section: Introduc4onmentioning

confidence: 99%

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Gated electron transport in rhodopsin and its relevance to GPCR activation

Gehrckens

Horsfield

Skoulakis

et al. 2019

Preprint

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We iden4fy, by density-func4onal theory calcula4ons, an electron donor-bridge-acceptor (DBA) complex within the highest resolu4on X-ray diffrac4on structures of rhodopsin. The donor is a conserved tryptophan, the acceptor is a zinc ion surrounded by a tryptophan, a his4dine and a conserved glutamate. The unusual environment of the zinc ion confers high electron affinity on the zinc site. The bridge is the re4nal which can exist either in the neutral aldimine (Schiff's base) or aldiminium (protonated) state. When the re4nal is unprotonated, no electron transfer occurs. Upon protona4on of the aldimine, the DBA complex conducts and a full electron charge is transferred from donor tryptophan to the zinc complex. This gated electron transfer creates the molecular equivalent of a tunnel triode. Since rhodopsin is the ancestor of GPCRs, we discuss the possible relevance of this gated electron transport to other GPCRs, in par4cular to olfactory receptors which have been proposed to use an electron tunneling mechanism to detect molecular vibra4ons.

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Section: Figure 11mentioning

confidence: 99%

Section: Introduc4onmentioning

confidence: 99%

Gated electron transport in rhodopsin and its relevance to GPCR activation

Gehrckens

Horsfield

Skoulakis

et al. 2019

Preprint

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“…7 However, the heterologous odour receptor expression in a kidney-derived cell line raised doubts about their functionality. 1 Altogether, a final explanation of the molecule-receptor interaction is not in sight, and further experimental tests of any model will support this important research goal.…”

Section: Introductionmentioning

confidence: 99%

“…1 Traditional views on the topic 2 have been challenged by recent findings, [3][4][5] but conclusive evidence could not be provided yet, leaving the debate widely open. [6][7][8][9] Odour perception initiates on the membrane of olfactory receptor neurons, where volatile odorants interact with olfactory receptor proteins triggering a signalling cascade.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8][9] Odour perception initiates on the membrane of olfactory receptor neurons, where volatile odorants interact with olfactory receptor proteins triggering a signalling cascade. As suggested by comparison with other receptors from the G protein-coupled receptor (GPCR) family, to which human odour receptors belong, 1 such interaction might rely purely on chemical binding, probing the size, shape, and functional groups of an odorant. This model is predominant in textbooks, and constitutes the framework within which the majority of research on olfaction is conducted.…”

Section: Introductionmentioning

confidence: 99%

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Testing odorant-receptor interaction theories in humans through discrimination of isotopomers

et al. 2017

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Odour reception takes place on the olfactory receptor neuron membrane, where molecular receptors interact with volatile odorant molecules. This interaction is classically thought to rely on chemical and structural features of the odorant, e.g. size, shape, functional groups. However, this model does not allow formulating a correct prediction for the smell of an odorant, suggesting that other molecular properties may play a role in the odour transduction process. An alternative model of olfaction maintains that odorant receptors can probe not only the structural and chemical features, but also the molecular vibration spectrum of the odorants. This constitutes the so-called vibration model of olfaction. According to this model, two isotopomers of the same molecule, i.e. two forms of the same molecule, one unaltered and one in which one or more hydrogen atoms are substituted with deuterium -which are therefore structurally and chemically identical, but with different molecular vibration spectra -would interact differently with an olfactory receptor, producing different olfactory perceptions in the brain. Here, we report on a duo-trio discrimination experiment conducted on human subjects, testing isotopomer pairs that have recently been shown to be differentially encoded in the honeybee brain.

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Sensory Perception of Non‐Deuterated and Deuterated Organic Compounds

Salthammer

Monegel

Schulz

et al. 2020

Chemistry A European J

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The chemical background of olfactory perception has been subject of intensive research, but no available model can fully explain the sense of smell. There are also inconsistent results on the role of the isotopology of molecules. In experiments with human subjects it was found that the isotope effect is weak with acetone and D 6 ‐acetone. In contrast, clear differences were observed in the perception of octanoic acid and D 15 ‐octanoic acid. Furthermore, a trained sniffer dog was initially able to distinguish between these isotopologues of octanoic acid. In chromatographic measurements, the respective deuterated molecule showed weaker interaction with a non‐polar liquid phase. Quantum chemical calculations give evidence that deuterated octanoic acid binds more strongly to a model receptor than non‐deuterated. In contrast, the binding of the non‐deuterated molecule is stronger with acetone. The isotope effect is calculated in the framework of statistical mechanics. It results from a complicated interplay between various thermostatistical contributions to the non‐covalent free binding energies and it turns out to be very molecule‐specific. The vibrational terms including non‐classical zero‐point energies play about the same role as rotational/translational contributions and are larger than bond length effects for the differential isotope perception of odor for which general rules cannot be derived.

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Molecular recognition in olfaction

Cited by 19 publications

References 113 publications

Gated electron transport in rhodopsin and its relevance to GPCR activation

Gated electron transport in rhodopsin and its relevance to GPCR activation

Testing odorant-receptor interaction theories in humans through discrimination of isotopomers

Sensory Perception of Non‐Deuterated and Deuterated Organic Compounds

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