0000000001167141
AUTHOR
Maud Sigoillot
showing 21 related works from this author
Strategy for recombinant expression of functional N-terminal domain of human T1R3 taste receptor produced in Escherichia Coli
2009
International audience
Activity and expression of drug metabolizing enzymes in olfactory mucosa of rats treated by hepatic inducers
2008
International audience; Several drug-metabolizing enzymes (DME), such as cytochrome P450- dependent monooxygenases (CYP) and transferases have been characterized in the olfactory epithelium. Some of them are preferentially expressed in this tissue, while others are similar to those present in the liver. The role of these enzymes remains unclear. Since the olfactory mucosa is in direct contact with the external environment, these enzymes can contribute to the detoxification of chemical compounds. In addition, these enzymes could be involved in the olfaction process, especially in the biotransformation of odorants. Indeed, the rapid inactivation and clearance of odorants is a prerequisite for…
Electrochemical detection of the 2-isobutyl-3-methoxypyrazine model odorant based on odorant-binding proteins: The proof of concept
2014
Abstract We developed an electrochemical assay for the detection of odorant molecules based on a rat odorant-binding protein (rOBP3). We demonstrated that rOBP3 cavity binds 2-methyl-1,4-naphtoquinone (MNQ), an electrochemical probe, as depicted from the decrease of its electrochemical signal, and deduced the dissociation constant, Kd MNQ = 0.5(± 0.2) μM. The amount of MNQ displaced from rOBP3 by 2-isobutyl-3-methoxypyrazine (IBMP), a model odorant molecule, was measured using square-wave voltammetry. The release of MNQ by competition led to an increase of the electrochemical response. In addition, this method allowed determination of the dissociation constant of rOBP3 for IBMP, Kd IBMP =…
The Crystal Structure of Gurmarin, a Sweet Taste–Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition
2018
International audience; Gurmarin is a highly specific sweet-taste suppressing protein in rodents that is isolated from the Indian plant Gymnemasylvestre. Gurmarin consists of 35 amino acid residues containing three intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.45 Å resolution and compare it with previously reported NMR solution structures. The atomic structure at this resolution allowed us to identify a very flexible region consisting of hydrophobic residues. Some of these amino acid residues had been identified as a putative binding site for the rat sweet taste receptor in a previous study. By combining alanine-scanning …
Recombinant expression, in vitro refolding, and biophysical characterization of the N-terminal domain of T1R3 taste receptor
2012
Facteur d'impact (5 ans) : 1,617Notoriété à 2 ans : Acceptable (biochem.res.methods); The sweet taste receptor is a heterodimeric receptor composed of the T1R2 and T1R3 subunits, while T1R1 and T1R3 assemble to form the umami taste receptor. T1R receptors belong to the family of class C G-protein coupled receptors (GPCRs). In addition to a transmembrane heptahelical domain, class C GPCRs have a large extracellular N-terminal domain (NTD), which is the primary ligand-binding site. The T1R2 and T1R1 subunits have been shown to be responsible for ligand binding, via their NTDs. However, little is known about the contribution of T1R3-NTD to receptor functions. To enable biophysical characteriza…
An efficient Escherichia coli expression system for the production of a functional N-terminal domain of the T1R3 taste receptor.
2012
http://www.landesbioscience.com/; International audience; Sweet taste is mediated by a dimeric receptor composed of two distinct subunits, T1R2 and T1R3, whereas the T1R1/T1R3 receptor is involved in umami taste perception. The T1R1, T1R2, and T1R3 subunits are members of the small family of class C G protein-coupled receptors (GPCRs). The members of this family are characterized by a large N-terminal domain (NTD), which is structurally similar to bacterial periplasmic-binding proteins and contains the primary ligand-binding site. In a recent study, we described a strategy to produce a functional dimeric human T1R3-NTD. Although the protein was expressed as inclusion bodies (IBs) using the …
Les inhibiteurs du goût sucré : perspectives thérapeutiques
2015
This review summarizes and discusses the current knowledge concerning the physiological role of the sweet taste receptor (T1R2/T1R3) and the potential therapeutic perspectives concerning its inhibition. The functional expression of the sweet taste receptor has also been described in many extra-oral tissues where it has been proposed that the receptor participated in the regulation of metabolic processes. The receptor has been highlighted in various organs such as the intestine, pancreas, bladder, brain, and more recently in the bone and adipose tissue. In the intestine, T1R2/T1R3 receptor has been shown to be involved in the detection of luminal glucose, cytokine release of certain hormones…
Les molécules odorantes, sapides et trigéminales
2012
National audience
Effects of typical inducers on olfactory xenobiotic-metabolizing enzyme, transporter, and transcription factor expression in rats.
2010
International audience; Several xenobiotic-metabolizing enzymes (XMEs) have been identified in the olfactory mucosa (OM) of mammals. However, the molecular mechanisms underlying the regulation of these enzymes have been little explored. In particular, information on the expression of the transcriptional factors in this tissue is quite limited. The aim of the present study was to examine the impact of five typical inducers, Aroclor 1254, 3-methylcholanthrene, dexamethasone, phenobarbital, and ethoxyquin, on the activities and mRNA expression of several XMEs in the OM and in the liver of rats. We also evaluated the effects of these treatments on the mRNA expression of transcription factors an…
Overexpression of recombinant gurmarin secreted by the yeast Pichia pastoris
2011
International audience
Expression and biophysical characterization of the human T1R1 taste receptor subunit
2011
Expression and biophysical characterization of the human T1R1 taste receptor subunit. 21. Congress of the european chemoreception research organisation (ECRO)
Le point sur... Perspectives thérapeutiques des inhibiteurs du goût sucré
2015
Nous percevons le goût sucré à l’aide d’un récepteur unique, appelé T1R2/T1R3. Ce récepteur nous permet de détecter tous les divers composés chimiques que nous percevons comme sucrés. De façon surprenante, des études récentes ont montré qu’il était présent dans de nombreux tissus et organes en dehors de la cavité orale. Parce qu’il joue un rôle dans le contrôle métabolique, ce récepteur représente une cible potentielle et prometteuse pour le traitement de l’obésité et des maladies métaboliques, telles que le diabète et l’obésité via notamment l’utilisation d’inhibiteurs spécifiques.
Resolution of the X-ray structure of gurmarin: new insights into the molecular mechanism of sweet taste receptor inhibition
2019
International audience
Étude biochimique des récepteurs aux goûts sucré et umami : Rôle des domaines N-terminaux et caractérisation d'un inhibiteur spécifique, la gurmarine
2011
The sweet taste receptor is a heterodimer composed of two subunits called T1R2 and T1R3 whereas the T1R1 and the T1R3 subunits form a heterodimeric receptor for umami taste (the savory taste of monosodium glutamate). Each subunit belongs to the class C of G protein-coupled receptors (GPCRs) and is constituted by a large extracellular Nterminal domain (NTD) linked to the transmembrane domain by a cysteine-rich region. The NTD is composed of two lobes separated by a cleft in which ligands bind. T1R1- and T1R2-NTDs are able to bind sweeteners and umami compounds respectively and undergo ligand-dependent conformational changes (Zhang et al., 2008 ; Nie et al., 2005). However, the relative contr…
Purification, biophysical characterization and first crystallization trials of the ligand-binding domain of the human T1R3 sweet taste receptor
2013
International audience
Flavor receptors
2011
National audience
Expression of functional N-terminal domain of human T1R2 taste receptor
2011
International audience
Expression and characterization of ligand-binding domain of T1R1 taste receptor
2010
International audience; Umami is the typical taste induced by monosodium glutamate,which is thought to be detected by a heterodimeric G-proteincoupled receptors, T1R1 and T1R3. The most unique feature ofumami taste is its potentiation by purine nucleotidemonophosphates (IMP, GMP), which also elicit umami taste bytheir own. Zhang et al. (Proc. Natl Acad. Sci. USA, 2008) haverecently proposed a cooperative ligand-binding model involvingT1R1 N-terminal domain (NTD), where L-glutamate (L-glu)binds close to the hinge region, and purine nucleotides bind to anadjacent site close to the opening of the Venus flytrap domain. Tofurther understand the structural basis of umami stimulirecognition by T1R…
Characterization of ligands for human T1R3 taste receptor
2010
National audience
Purification and characterization of recombinant gurmarin secreted by the yeast Pichia pastoris
2010
National audience
The X-ray structure of gurmarin provide new insights into amino acid residues essential for inhibition of the rat sweet taste receptor
2018
International audience; Gurmarin is a polypeptide isolated from the Indian plant Gymnema sylvestre, which specifically suppresses sweet taste in rodents without affecting responses to other basic taste stimuli, such as HCl, NaCl, and quinine. Although the exact mechanism of gurmarin inhibition is not known, it has been shown that gurmarin acts via the T1R2/T1R3 sweet taste receptor. The gurmarin molecule is made of 35 amino-acid residues and three intramolecular disulfide bridges. We report herein the 1.45 Å X-ray structure of gurmarin heterologously produced using the yeast Pichia pastoris. The structure revealed a typical knottin fold, which is compared with previously reported NMR soluti…