G-protein coupled receptors (GPCRs) represent one of the most important families of drug targets in pharmaceutical development. GLIDA is a public GPCR-related Chemical Genomics database that is primarily focused on the integration of information between GPCRs and their ligands. It provides interaction data between GPCRs and their ligands, along with chemical information on the ligands, as well as biological information regarding GPCRs. These data are connected with each other in a relational database, allowing users in the field of Chemical Genomics research to easily retrieve such information from either biological or chemical starting points. GLIDA includes a variety of similarity search functions for the GPCRs and for their ligands. Thus, GLIDA can provide correlation maps linking the searched homologous GPCRs (or ligands) with their ligands (or GPCRs). By analyzing the correlation patterns between GPCRs and ligands, we can gain more detailed knowledge about their conserved molecular recognition patterns and improve drug design efforts by focusing on inferred candidates for GPCR-specific drugs. This article provides a summary of the GLIDA database and user facilities, and describes recent improvements to database design, data contents, ligand classification programs, similarity search options and graphical interfaces. GLIDA is publicly available at http://pharminfo.pharm.kyoto-u.ac.jp/services/glida/. We hope that it will prove very useful for Chemical Genomics research and GPCR-related drug discovery.
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http://dx.doi.org/10.1093/nar/gkm948 | DOI Listing |
Chembiochem
January 2025
University of Teramo: Universita degli Studi di Teramo, Veterinary Medicine, Piano d'Accio snc, 64100, Teramo, ITALY.
In this study, we employed a novel fluorescent probe, RO7304924-which selectively targets cannabinoid 2 receptor (CB2R)-to assess the lateral mobility of CB2R within the plasma membrane of Chinese hamster ovary cells stably expressing a functional, untagged receptor variant. Utilizing confocal fluorescence recovery after photobleaching (FRAP), we quantified the diffusion coefficient and mobile fraction of CB2R, thereby demonstrating the efficacy of RO7304924 as an innovative tool for elucidating the dynamics of this major endocannabinoid-binding G protein-coupled receptor. Our present findings highlight the potential of combining advanced ligand-based fluorescent probes with FRAP for future investigations into the biochemical details of CB2R mobility in living cells, and its impact on receptor-dependent cellular processes.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
January 2025
Department of Medicinal Chemistry and Institute for Translational Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, United States.
Opioid agonist ligands bind opioid receptors and stimulate downstream signaling cascades for various biological processes including pain and reward. Historically, before cloning the receptors, muscle contraction assays using isolated organ tissues were used followed by radiolabel ligand binding assays on native tissues. Upon cloning of the opioid G protein-coupled receptors (GPCRs), cell assays using transfected opioid receptor DNA plasmids became the standard practice including S-GTPγS functional and cAMP based assays.
View Article and Find Full Text PDFArch Med Res
January 2025
Programa de Investigación de Cancer de Mama, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico. Electronic address:
Na⁺/H⁺ exchanger regulatory factor 2 (NHERF2) is a nucleocytoplasmic protein initially identified as a regulator of membrane-bound sodium-hydrogen exchanger 3 (NHE3). In the cytoplasm, NHERF2 regulates the activity of G protein-coupled receptors (GPCRs), including beta-2 adrenergic receptor (2β-AR), lysophosphatidic acid receptor 2, and parathyroid hormone type 1 receptor. In the nucleus, NHERF2 acts as a coregulator of transcription factors such as sex-determining region Y protein (SRY), involved in male sex determination, and estrogen receptor alpha (ERα).
View Article and Find Full Text PDFJ Vis Exp
December 2024
Department of Ophthalmology and Visual Neurosciences, University of Minnesota;
G protein-coupled receptors (GPCRs) are a superfamily of transmembrane proteins that initiate signaling cascades through activation of its G protein upon association with its ligand. In all mammalian vision, rhodopsin is the GPCR responsible for the initiation of the phototransduction cascade. Within photoreceptors, rhodopsin is bound to its chromophore 11-cis-retinal and is activated through the light-sensitive isomerization of 11-cis-retinal to all-trans-retinal, which activates the transducin G protein, resulting in the phototransduction cascade.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Osaka 920-1192, Japan.
G protein-coupled receptors (GPCRs) are essential cell surface proteins involved in transducing extracellular signals into intracellular responses, regulating various physiological processes. This study validated the use of the Tango assay, a sensitive method for detecting GPCR activation, in Schneider 2 (S2) cells, focusing on the human Dopamine Receptor D4 (DRD4). Plasmids encoding the LexA-tagged human DRD4 receptor and a luciferase reporter were co-transfected into S2 cells and stimulated with dopamine.
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