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Title: The role of metals in mammalian olfaction of low molecular weight organosulfur compounds

Abstract

While suggestions concerning the possible role of metals in olfaction and taste date back 50 years, only recently has it been possible to confirm these proposals with experiments involving individual olfactory receptors (ORs). A detailed discussion of recent experimental results demonstrating the key role of metals in enhancing the response of human and other vertebrate ORs to specific odorants is presented against the backdrop of our knowledge of how the sense of smell functions both at the molecular and whole animal levels. This review emphasizes the role of metals in the detection of low molecular weight thiols, sulfides, and other organosulfur compounds, including those found in strong-smelling animal excretions and plant volatiles, and those used in gas odorization. Alternative theories of olfaction are described, with evidence favoring the modified “shape” theory. The use of quantum mechanical/molecular modeling (QM/MM), site-directed mutagenesis and saturation-transfer-difference (STD) NMR is discussed, providing support for biological studies of mouse and human receptors, MOR244-3 and OR OR2T11, respectively. Copper is bound at the active site of MOR244-3 by cysteine and histidine, while cysteine, histidine and methionine are involved with OR2T11. The binding pockets of these two receptors are found in different locations in the three-dimensional seven transmembranemore » models. Another recently deorphaned human olfactory receptor, OR2M3, highly selective for a thiol from onions, and a broadly-tuned thiol receptor, OR1A1, are also discussed. Other topics covered include the effects of nanoparticles and heavy metal toxicants on vertebrate and fish ORs, intranasal zinc products and the loss of smell (anosmia).« less

Authors:
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [3]; ORCiD logo [4]; ORCiD logo [2]
  1. Department of Chemistry; University at Albany; State University of New York; Albany; USA
  2. Department of Chemistry; Yale University; New Haven; USA
  3. Department of Molecular Genetics and Microbiology; Department of Neurobiology; Duke Institute for Brain Sciences; Duke University Medical Center; Durham
  4. Institutes of Health Sciences; Shanghai Jiaotong University School of Medicine; Shanghai Institutes for Biological Science of Chinese Academy of Sciences; Shanghai 200031; China
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory-National Energy Research Scientific Computing Center
Sponsoring Org.:
USDOE
OSTI Identifier:
1492957
Resource Type:
Journal Article
Journal Name:
Natural Product Reports
Additional Journal Information:
Journal Volume: 34; Journal Issue: 5; Journal ID: ISSN 0265-0568
Country of Publication:
United States
Language:
English

Citation Formats

Block, Eric, Batista, Victor S., Matsunami, Hiroaki, Zhuang, Hanyi, and Ahmed, Lucky. The role of metals in mammalian olfaction of low molecular weight organosulfur compounds. United States: N. p., 2017. Web. doi:10.1039/c7np00016b.
Block, Eric, Batista, Victor S., Matsunami, Hiroaki, Zhuang, Hanyi, & Ahmed, Lucky. The role of metals in mammalian olfaction of low molecular weight organosulfur compounds. United States. doi:10.1039/c7np00016b.
Block, Eric, Batista, Victor S., Matsunami, Hiroaki, Zhuang, Hanyi, and Ahmed, Lucky. Sun . "The role of metals in mammalian olfaction of low molecular weight organosulfur compounds". United States. doi:10.1039/c7np00016b.
@article{osti_1492957,
title = {The role of metals in mammalian olfaction of low molecular weight organosulfur compounds},
author = {Block, Eric and Batista, Victor S. and Matsunami, Hiroaki and Zhuang, Hanyi and Ahmed, Lucky},
abstractNote = {While suggestions concerning the possible role of metals in olfaction and taste date back 50 years, only recently has it been possible to confirm these proposals with experiments involving individual olfactory receptors (ORs). A detailed discussion of recent experimental results demonstrating the key role of metals in enhancing the response of human and other vertebrate ORs to specific odorants is presented against the backdrop of our knowledge of how the sense of smell functions both at the molecular and whole animal levels. This review emphasizes the role of metals in the detection of low molecular weight thiols, sulfides, and other organosulfur compounds, including those found in strong-smelling animal excretions and plant volatiles, and those used in gas odorization. Alternative theories of olfaction are described, with evidence favoring the modified “shape” theory. The use of quantum mechanical/molecular modeling (QM/MM), site-directed mutagenesis and saturation-transfer-difference (STD) NMR is discussed, providing support for biological studies of mouse and human receptors, MOR244-3 and OR OR2T11, respectively. Copper is bound at the active site of MOR244-3 by cysteine and histidine, while cysteine, histidine and methionine are involved with OR2T11. The binding pockets of these two receptors are found in different locations in the three-dimensional seven transmembrane models. Another recently deorphaned human olfactory receptor, OR2M3, highly selective for a thiol from onions, and a broadly-tuned thiol receptor, OR1A1, are also discussed. Other topics covered include the effects of nanoparticles and heavy metal toxicants on vertebrate and fish ORs, intranasal zinc products and the loss of smell (anosmia).},
doi = {10.1039/c7np00016b},
journal = {Natural Product Reports},
issn = {0265-0568},
number = 5,
volume = 34,
place = {United States},
year = {2017},
month = {1}
}

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