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Communication Dans Un Congrès Année : 2016

Interactions of human nasal glutathione transferases with odorants.


Odorant metabolizing enzymes (OME) and other proteins including odorant-binding proteins participate to a series of processes modulating the odor perception. These proteins are thought to respectively participate in odorant degradation or transport. The odorant metabolization may result in (i) the formation of new odorants (metabolites), (ii) changes in odorant bioavailability (iii) the receptor signal termination. Different OMEs as carboxylesterases or glutathione transferases (GSTs) have been shown to be involved in the mammalian olfactory process. GSTs are ubiquitous enzymes present in many tissues as liver, brain, olfactory mucosa or mucus. GSTs can be divided in six gene-independent family including the GSTA1 and GSTP1, both found in the human olfactory mucus. GSTs exhibits different enzymatic functions, including the conjugation of a variety of hydrophobic compounds to glutathione or isomerisation reaction, but these enzymes are also involved in molecules transport. We recently demonstrated in vitro the dual function of the human GSTA1 toward odorant molecules: odorant glutathione-conjugation and odorant transporter. Here, we deciphered the structure function relationship between GSTA1 and odorants. To reach this goal, we heterologously expressed human GSTA1 in E. coli. The recombinant protein was purified with purity greater than 99%. A large screen of odorants (different chemical families, such as: alcohol, ketone, aldehyde, acid molecules) interacting with GSTA1 was performed. The analysis was then refined to investigate, stereoselectivity (D, L limonene), chain length (fatty acid, ketone series), nature or the chemical function of the odorants structure in the interaction with GSTA1. Our work brings new elements to understand the binding mechanisms of GSTs, and their potential role in the olfactory peri-receptor events.

Dates et versions

hal-01398373 , version 1 (17-11-2016)



Fabrice Neiers, Jean-Marie Heydel, Loïc Briand. Interactions of human nasal glutathione transferases with odorants.. 25th Annual Meeting of the European-Chemoreception-Research-Organization (ECRO), European Chemorecept Res Org, Sep 2015, Istanbul, Turkey. pp.422-422, ⟨10.1093/chemse/bjw019⟩. ⟨hal-01398373⟩
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