Molecular Basis of Mammalian Odor Discrimination: A Status Report

Block, Eric

doi:10.1021/acs.jafc.8b04471

Cited by 51 publications

(53 citation statements)

References 155 publications

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“…The consensus sequence "HxxC[DE]" can be found in 74% of all human ORs, which led them to propose ORs as metalloproteins [28]. The role of metals in mammalian olfaction is the subject of recent reviews [35,36].…”

Section: Introductionmentioning

confidence: 99%

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

Haag

Ahmed

Reiss

et al. 2019

Cell. Mol. Life Sci.

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Sulfur-containing compounds within a physiological relevant, natural odor space, such as the key food odorants, typically constitute the group of volatiles with the lowest odor thresholds. The observation that certain metals, such as copper, potentiate the smell of sulfur-containing, metal-coordinating odorants led to the hypothesis that their cognate receptors are metalloproteins. However, experimental evidence is sparse-so far, only one human odorant receptor, OR2T11, and a few mouse receptors, have been reported to be activated by sulfur-containing odorants in a copper-dependent way, while the activation of other receptors by sulfur-containing odorants did not depend on the presence of metals. Here we identified an evolutionary conserved putative copper interaction motif CC/CSSH, comprising two copper-binding sites in TMH5 and TMH6, together with the binding pocket for 3-mercapto-2-methylpentan-1-ol in the narrowly tuned human receptor OR2M3. To characterize the copper-binding motif, we combined homology modeling, docking studies, site-directed mutagenesis, and functional expression of recombinant ORs in a cell-based, real-time luminescence assay. Ligand activation of OR2M3 was potentiated in the presence of copper. This effect of copper was mimicked by ionic and colloidal silver. In two broadly tuned receptors, OR1A1 and OR2W1, which did not reveal a putative copper interaction motif, activation by their most potent, sulfur-containing key food odorants did not depend on the presence of copper. Our results suggest a highly conserved putative copper-binding motif to be necessary for a copper-modulated and thiol-specific function of members from three subfamilies of family 2 ORs.

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Section: Introductionmentioning

confidence: 99%

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

Haag

Ahmed

Reiss

et al. 2019

Cell. Mol. Life Sci.

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“…So far, about 230 volatiles have been identified as so-called “key food odorants” (KFOs) [ 16 ]. These KFOs are the best natural agonists for approximately 400 human olfactory receptors (ORs) [ 17 ]. Aroma research has shown that the distinctive aroma for 227 different food commodities is determined by a relatively small subset of 3 to 40 KFOs.…”

Section: The Concept Of the Chemical Odorant Spacementioning

confidence: 99%

“…The biochemical mechanism for perception of odor-active phenols is now well understood and is a remarkable piece of Nobel Prize winning research (Nobel Prize in Physiology or Medicine 2004 for Richard Axel and Lina B. Buck for their discoveries of odorant receptors and the organization of the olfactory system) [ 17 ]. Odor perception is initiated by an odorant molecule binding to receptors that are located in the cilia of olfactory receptor cells in the nasal epithelium.…”

Section: Perception Of Odor-active Phenolsmentioning

confidence: 99%

Volatile Phenols—Important Contributors to the Aroma of Plant-Derived Foods

Schieber

Wüst

2020

Molecules

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Volatile phenols like phenylpropanoid and benzoid compounds originate from the aromatic amino acid phenylalanine, which is biosynthesized via the shikimate/arogenate pathway. These volatile compounds contribute to the aroma of a number of economically important plant-derived foods like herbs, spices and fruits. The sequestration of numerous phenylpropanoid and benzoid compounds as glycosides occurs widely in fruits, and this pool represents an important source of flavor that can be released during storage and processing. Therefore, this review will provide an overview of the biosynthesis of free and glycosylated phenylpropanoid and benzoid compounds and their reactions during food processing, which both lead to the generation of odor-active volatile phenols in plant-derived foods.

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“…The perception of an odor's quality is a result of combinatorial coding [2], whereby an odorant can interact with several ORs, while ORs can be activated by several structurally diverse odorants. Despite advances in the understanding of olfactory perception, olfactory coding remains poorly understood [3,4], especially in the case of a mixture of odorants. Still, odors perceived in our environment are mainly the result of mixtures of odorants [5].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Characteristics of an Aroma-Blending Mixture by Investigating the Network of Shared Odors and the Molecular Features of Their Related Odorants

et al. 2020

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The perception of aroma mixtures is based on interactions beginning at the peripheral olfactory system, but the process remains poorly understood. The perception of a mixture of ethyl isobutyrate (Et-iB, strawberry-like odor) and ethyl maltol (Et-M, caramel-like odor) was investigated previously in both human and animal studies. In those studies, the binary mixture of Et-iB and Et-M was found to be configurally processed. In humans, the mixture was judged as more typical of a pineapple odor, similar to allyl hexanoate (Al-H, pineapple-like odor), than the odors of the individual components. To explore the key features of this aroma blend, we developed an in silico approach based on molecules having at least one of the odors—strawberry, caramel or pineapple. A dataset of 293 molecules and their related odors was built. We applied the notion of a “social network” to describe the network of the odors. Additionally, we explored the structural properties of the molecules in this dataset. The network of the odors revealed peculiar links between odors, while the structural study emphasized key characteristics of the molecules. The association between “strawberry” and “caramel” notes, as well as the structural diversity of the “strawberry” molecules, were notable. Such elements would be key to identifying potential odors/odorants to form aroma blends.

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Molecular Basis of Mammalian Odor Discrimination: A Status Report

Cited by 51 publications

References 155 publications

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

Copper-mediated thiol potentiation and mutagenesis-guided modeling suggest a highly conserved copper-binding motif in human OR2M3

Volatile Phenols—Important Contributors to the Aroma of Plant-Derived Foods

Exploring the Characteristics of an Aroma-Blending Mixture by Investigating the Network of Shared Odors and the Molecular Features of Their Related Odorants

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