Introducing a New Model of Sweet Taste Receptor, a Class C G-protein Coupled Receptor (C GPCR)

Kashani-Amin, Elaheh; Sakhteman, Amirhossein; Larijani, Bagher; Ebrahim‐Habibi, Azadeh

doi:10.1007/s12013-019-00872-7

Cited by 14 publications

(11 citation statements)

References 56 publications

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“…Thereafter, the structural dynamics of the Reb-A complexed with the human T1R2 homolog was analysed by performing molecular dynamics simulations 83 – 87 and free binding energy calculations 88 , 89 , which have proved to be very useful and successful in understanding the molecular basis of small molecules interacting with different biological targets including GPCR agonists 90 , 91 and sweet taste receptors 86 , 87 . An MD simulation provides useful structural and energetic information about the interaction between the inhibitors (or molecules) and the target receptor.…”

Section: Resultsmentioning

confidence: 99%

An in-silico layer-by-layer adsorption study of the interaction between Rebaudioside A and the T1R2 human sweet taste receptor: modelling and biosensing perspectives

Arodola

Kanchi

Hloma

et al. 2020

Sci Rep

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The human sweet taste receptor (T1R2) monomer—a member of the G-protein coupled receptor family that detects a wide variety of chemically and structurally diverse sweet tasting molecules, is known to pose a significant threat to human health. Protein that lack crystal structure is a challenge in structure-based protein design. This study focused on the interaction of the T1R2 monomer with rebaudioside A (Reb-A), a steviol glycoside with potential use as a natural sweetener using in-silico and biosensing methods. Herein, homology modelling, docking studies, and molecular dynamics simulations were applied to elucidate the interaction between Reb-A and the T1R2 monomer. In addition, the electrochemical sensing of the immobilised T1R2-Reb-A complex with zinc oxide nanoparticles (ZnONPs) and graphene oxide (GO) were assessed by testing the performance of multiwalled carbon nanotube (MWCNT) as an adsorbent experimentally. Results indicate a strong interaction between Reb-A and the T1R2 receptor, revealing the stabilizing interaction of the amino acids with the Reb-A by hydrogen bonds with the hydroxyl groups of the glucose moieties, along with a significant amount of hydrophobic interactions. Moreover, the presence of the MWCNT as an anchor confirms the adsorption strength of the T1R2-Reb-A complex onto the GO nanocomposite and supported with electrochemical measurements. Overall, this study could serve as a cornerstone in the development of electrochemical immunosensor for the detection of Reb-A, with applications in the food industry.

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Section: Resultsmentioning

confidence: 99%

An in-silico layer-by-layer adsorption study of the interaction between Rebaudioside A and the T1R2 human sweet taste receptor: modelling and biosensing perspectives

Arodola

Kanchi

Hloma

et al. 2020

Sci Rep

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“…Likewise, Udagawa et al [22] detected TAS1R3, but not TAS1R2 or TAS1R1, in isolated rat and mouse b-islets, INS-1 cells and MIN6 cells by qPCR. Furthermore, while the TAS1R2 VFD is recognized as the orthosteric-binding site of the STR [16,23,24], the TAS1R3 VFD also accommodates sweet ligands [16,25]. Unfortunately, many of the claims of apparent homo-or monomeric species, particularly in vivo, are based upon indirect evidence (e.g., simply detecting one subunit but not the other in a tissue or cell), poorly validated tools (e.g., antibodies used in the absence of knockout tissue controls) or partial knockdown of T1R3.…”

Section: Structural Characteristics Of the Sweet Taste Receptormentioning

confidence: 99%

Critically evaluating sweet taste receptor expression and signaling through a molecular pharmacology lens

et al. 2021

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The class C G protein-coupled sweet taste receptor (STR) is responsible for the perception of sweet-tasting molecules. Considered an obligate heterodimer, it consists of taste 1 receptor 2 and taste 1 receptor 3 subunits. Interest in the STR has steadily grown, especially since its discovery in extraoral tissues hints at a metabolic role for the receptor. It is now known that many pharmacologically exploitable binding sites exist across the extracellular and transmembrane regions of both subunits of the STR, indicative of its potential amenability to pharmacotherapeutic modulation. In this review, we briefly describe the structural characteristics and functional relevance of the STR. Then, from a molecular pharmacology perspective, we dissect the research surrounding the regulation of STR surface expression and signal transduction, in both oral and extraoral tissues, and discuss the potential for the exploitation of biased agonists for the STR. We find that despite 20 years of research into the STR, the target remains frustratingly enigmatic. Not only are the mechanisms controlling and regulating the surface expression of the STR unclear, but also research into the full repertoire of signaling partners of the STR is at present inconclusive. Critically, the influence of receptor polymorphisms (including those associated with sugar consumption) on the molecular pharmacology of the receptor remains hitherto unexplored. Finally, we provide recommendations on the reporting of reference sequence identification numbers to avoid incorrect attribution of wildtype to these biologically significant polymorphisms, which we argue may have led to some of the inconsistencies in the field.

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“…In order to design appropriate ligands for this receptor, a three-dimensional structure is needed, but since the human receptor structure is still not experimentally elucidated, in silico (molecular modeling) methods were used in this case. First, a new model of STR structure was developed [54]. Extensive docking experiments on the model revealed presence of carbohydrate binding modules as structural and functional motifs [55], which is applicable in further characterization of the binding site.…”

Section: Glucose Homeostasis and Related Metabolic Conditions Disordersmentioning

confidence: 99%

“…First, a new model of STR structure was developed [54]. Extensive docking experiments on the model revealed presence of carbohydrate binding modules as structural and functional motifs [55], which is applicable in further characterization of the binding site. Docking was performed on an ensemble of STR structures obtained by running a molecular dynamics simulation (MDS) experiment.…”

Section: Glucose Homeostasis and Related Metabolic Conditions Disordersmentioning

confidence: 99%

Modeling and simulation in medical sciences: an overview of specific applications based on research experience in EMRI (Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences)

Ebrahim‐Habibi

Kashani-Amin

Larijani

2021

J Diabetes Metab Disord

Self Cite

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The concomitant use of various types of models (in silico, in vitro, and in vivo) has been exemplified here within the context of biomedical researches performed in the Endocrinology and Metabolism Research Institute (EMRI) of Tehran University of Medical Sciences. Two main research aeras have been discussed: the search for new small molecules as therapeutics for diabetes and related metabolic conditions, and diseases related to protein aggregation. Due to their multidisciplinary nature, the majority of these studies have needed the collaboration of different specialties. In both cases, a brief overview of the subject is provided through literature examples, and sequential use of these methods is described.

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Introducing a New Model of Sweet Taste Receptor, a Class C G-protein Coupled Receptor (C GPCR)

Cited by 14 publications

References 56 publications

An in-silico layer-by-layer adsorption study of the interaction between Rebaudioside A and the T1R2 human sweet taste receptor: modelling and biosensing perspectives

An in-silico layer-by-layer adsorption study of the interaction between Rebaudioside A and the T1R2 human sweet taste receptor: modelling and biosensing perspectives

Critically evaluating sweet taste receptor expression and signaling through a molecular pharmacology lens

Modeling and simulation in medical sciences: an overview of specific applications based on research experience in EMRI (Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences)

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