Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
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For several decades, significant efforts have been made in developing artificial taste sensors to recognize the five basic tastes. So far, the well-established taste sensor is an E-tongue, which is constructed with polymer and lipid membranes. However, the previous artificial taste sensors have limitations in various food, beverage, and cosmetic industries because of their failure to mimic human taste reception. There are many interactions between tastants. Therefore, detecting the interactions in a multiplexing system is required. Herein, we developed a duplex bioelectronic tongue (DBT) based on graphene field-effect transistors that were functionalized with heterodimeric human umami taste and sweet taste receptor nanovesicles. Two types of nanovesicles, which have human T1R1/T1R3 for the umami taste and human T1R2/T1R3 for the sweet taste on their membranes, immobilized on micropatterned graphene surfaces were used for the simultaneous detection of the umami and sweet tastants. The DBT platform led to highly sensitive and selective recognition of target tastants at low concentrations (ca. 100 nM). Moreover, our DBT was able to detect the enhancing effect of taste enhancers as in a human taste sensory system. This technique can be a useful tool for the detection of tastes instead of sensory evaluation and development of new artificial tastants in the food and beverage industry.
ACS Nano 2016 08 23
PMID:Duplex Bioelectronic Tongue for Sensing Umami and Sweet Tastes Based on Human Taste Receptor Nanovesicles. 2732 79

T1R2/T1R3 belongs to G protein coupled receptors, which recognizes diverse natural and synthetic sweeteners. A novel class of positive allosteric modulators (PAMs) of T1R2/T1R3 was identified through high-throughput screening campaign. Comparing the structure of the potent compound with previously known PAM, we classified the structure of known PAM into three parts, defined as "head", "linker", and "tail". We then investigated the linker-tail structure. It was suggested by molecular docking models of T1R2/T1R3 that an amine that we introduced in the tail was the key for interaction with the receptor binding pocket. We thus synthesized various molecules and found unnatural tripeptide-PAMs, which potently enhance the sweetness of sucrose in sensory evaluation tests.
ACS Med Chem Lett 2019 May 09
PMID:Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3. 3109 2

Sweet taste receptor, a heterodimer belonging to the class C G-protein coupled receptor (GPCR) family and composed of the T1R2 and T1R3 subunits, is responsible for the perception of natural sugars, sweet proteins, various d-amino acids, as well as artificial sweeteners. Despite the critical importance of the sweet receptor not only in mediating gustation but also in its role in the food industry, the architecture of the T1R2-T1R3 complex and the mechanism by which extracellular stimuli induce conformational changes that are propagated to the intracellular milieu, i.e., the signal transduction pathway, remain largely unknown. Here, we constructed and characterized a full-length structural model of the T1R2-T1R3 receptor, including both the transmembrane (TM) and extracellular (EC) domains of the heterodimer, using comparative modeling and extensive all-atom molecular dynamics simulations. Several heterodimer interfaces were first examined for the TM domain, and conformational changes occurring at the intracellular side and associated with the receptor's activation were characterized. From the analysis on the simulated data, putative allosteric binding sites for ligands, ions, and cholesterol were proposed. Also, insights into the protein interface of the TM domain upon activation are provided. The EC domain of the heterodimer, including both the Venus flytrap and cysteine-rich domains, was also investigated. Several important intersubunit interactions located at regions responsible for the receptor's proper function were observed, which resemble those recently identified in other class C GPCR members. Integration of the results from the TM and EC domains facilitates the generation of a full-length T1R2-T1R3 receptor. These findings along with the full-length structural model of the T1R2-T1R3 receptor provide a structural framework that may assist in understanding the mechanistic details associated with the receptor activation process for the sweet T1R2-T1R3 receptor as well as other members of the same family.
ACS Chem Neurosci 2019 11 20
PMID:Modeling and Structural Characterization of the Sweet Taste Receptor Heterodimer. 3155 64