Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 25 bitter taste receptors (T2Rs) in humans are novel players in mediating host-pathogen responses in the airways and innate immunity. The chemosensory T2Rs are expressed in different extraoral tissues and perform diverse pathophysiological roles from mediating bronchodilation to detecting bacterial infection in the airways. T2Rs were suggested to be activated by multiple bacterial quorum sensing molecules (QSMs). However, whether bacterial QSMs bind to T2Rs and the structural features on T2Rs has not yet been characterized. Here, we analyzed the taste sensory profiles of QSMs including acyl homoserine lactones (C4-AHL, C8-AHL, and 3-oxo-C12-AHL) and hydroxyquinolones (HHQ and NHQ) predominantly secreted by Gram-negative bacteria and characterized the candidate T2Rs interacting with different QSMs using structure-function approaches. The potency of the above QSMs for T2Rs significantly expressed in the airways, namely T2R4, T2R14, and T2R20, was characterized. 3-Oxo-C12-AHL activated T2R4, T2R14, and T2R20, while C8-AHL activated T2R4 and T2R14 with strong potency. The T2R amino acid residues involved in the interactions were characterized by molecular-model-guided site-directed mutagenesis. AHLs bind to a similar orthosteric site present on the extracellular surface in all three T2Rs with significant contributions from residues in extracellular loop 2. Our results reveal the mode of binding of AHLs for different T2Rs and provide biochemical insights into their interactions. This study will facilitate mechanistic studies aimed at understanding the role of these T2Rs as "sensors" of bacteria and in host-pathogen interactions.
ACS Infect Dis 2018 07 13
PMID:Characterization of the Binding Sites for Bacterial Acyl Homoserine Lactones (AHLs) on Human Bitter Taste Receptors (T2Rs). 2979 89

Bitter taste substances commonly represent a signal of toxicity. Fast and reliable detection of bitter molecules improves the safety of foods and beverages. Here, we report a biosensor using an easily accessible and cost-effective odorant-binding protein (OBP) of Drosophila melanogaster as a biosensitive material for the detection of bitter molecules. Based on the theoretical evaluation of the protein-ligand interaction, binding energies between the OBP and bitter molecules were calculated via molecular docking for the prediction and verification of binding affinities. Through one-step reduction, gold nanoparticles (AuNPs) and reduced graphene oxide (rGO) were deposited on the screen-printed electrodes for improving the electrochemical properties of electrodes. After the electrodes were immobilized with OBPs via layer-by-layer self-assembly, typical bitter molecules, such as denatonium, quinine, and berberine, were investigated through electrochemical impedance spectroscopy. The bitter molecules showed significant binding properties to the OBP with linear response concentrations ranging from 10-9 to 10-6 mg/mL. Therefore, the OBP-based biosensor offered powerful analytic techniques for the detection of bitter molecules and showed promising applications in the field of bitter taste evaluation.
ACS Omega 2020 Oct 27
PMID:Detection of Bitter Taste Molecules Based on Odorant-Binding Protein-Modified Screen-Printed Electrodes. 3313 17