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August 2022 Production of human A 2A AR in lipid nanodiscs for 19 F-NMR and single-molecule fluorescence adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule fluorescence A2AAR and assembly of A2AAR in lipid nanodiscs and procedures for incorporation of either 19F-NMR or fluorescence

adenosine receptor (A2AAR), a class A G protein-coupled receptor (GPCR) for 19F-NMR and single-molecule fluorescence A2AAR and assembly of A2AAR in lipid nanodiscs and procedures for incorporation of either 19F-NMR or fluorescence

eyJ1IjoiaHR0cHM6Ly9kb2kub3JnLzEwLjExMTEvYnBoLjcwMDcyIiwiciI6ImUyZGZlOTFjLTM5YzgtNDA5Yi04NTUyLWI5NjUwNGRlNzc4MyIsIm0iOiJtYWlsX2xwIiwiYyI6IjAwMDAwMDAwLTAwMDAtMDAwMC0wMDAwLTAwMDAwMDAwMDAwMCJ9 The B2D consortium revives biodiversity as a source for selective GPCR ligands

Visualizing GLP-1 & GIP Receptors in Islets and Brain Understanding incretin biology depends on more than ligand David Hodson walks through how his team uses fluorescence tools and chemically engineered ligands to Fluorescent ligand engineering clarifies receptor behavior that cell lines can’t reveal.

Instead of forcing antibodies to do what they weren’t built for, JB’s group engineered fluorescent ligands cryo-EM data arrived — a structure solved through the same collaborative network that had built the fluorescent

GPCRs are present in a range of conformations, and the binding of a ligand, as well as interactions with Gαs from human erythrocytes led to an elevation in GTPase activity of Gαs without the presence of a ligand GPCR ligands pharmacology The impact of a ligand on a receptor's structure and biophysical attributes , and consequently on the biological response, is referred to as ligand efficacy. Natural and synthetic ligands can be categorized into four distinct efficacy classes: 1) full agonists

Molecular Modeling Study of a Receptor-Orthosteric Ligand-Allosteric Modulator Signaling Complex. Methods & Updates in GPCR Research Development and Characterization of a Highly Selective Turn-On Fluorescent Ligand for β3-Adrenergic Receptor.

Methods & Updates in GPCR Research Fluorescent Ligands Enable Target Engagement Studies for the Intracellular Reviews, GPCRs, and more Interplay of thermodynamics and evolution within the ternary ligand-GPCR-G protein

Isoform- and ligand-specific modulation of the adhesion GPCR ADGRL3/Latrophilin3 by a synthetic binder Development and Characterization of a Highly Selective Turn-On Fluorescent Ligand for β3-Adrenergic Receptor

C-X-C motif chemokine ligand 12 (CXCL12) has two receptors: C-X-C chemokine motif receptor 4 (CXCR4) We also synthesized a series of small molecule ligands which acted as selective agonists for ACKR3 as The development of more selective ACKR3 ligands should allow us to better appreciate the unique roles In this study, novel selective ligands for ACKR3 were discovered and the site of interactions between

October 2022 Structural perspectives on the mechanism of signal activation, ligand selectivity and allosteric tissue response to a given dose of the hormone or its antagonist depends on receptors that engage the ligand Thus, we need to know much more about the structures of receptor-ligand complexes at high resolution. , X-ray structures of both AngII receptors (AT1 and AT2 receptors) bound to peptide and non-peptide ligands Constituent structural motifs cooperatively transform ligand selectivity into specific functions, thus

Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. structures, combined with computational analyses, provide insights into the unique and complex process of ligand

Drugs, and more A snake toxin as a theranostic agent for the type 2 vasopressin receptor Small-Molecule Fluorescent Ligands for the CXCR4 Chemokine Receptor.

Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. structures, combined with computational analyses, provide insights into the unique and complex process of ligand

The real friction point lies downstream : translating receptor–ligand interactions into actionable development Allosteric modulators and biased ligands aren’t exotic outliers—they’re increasingly common outcomes

Depending on which ligand activates a receptor, it can engage different intracellular transducers. Ligands eliciting biased signalling may constitute better drugs with higher efficacy and fewer adverse However, ligand bias is very complex, making reproducibility and description challenging. Here, we provide guidelines and terminology for any scientists to design and report ligand bias experiments receptor research and drug discovery communities continue to advance our understanding and exploitation of ligand

A variety of ligands for CB1 receptors have been developed as promising drug candidates for the treatment receptor in different functional states have significantly improved our molecular understanding of CB1 ligand These advances have paved the way for development of novel ligands for different therapeutic applications review, we describe the structural determinants for modulation of CB1 receptors by different types of ligands

less side effects, and tools to explore the ORs nature and function, various (poly)pharmacological ligand That is, besides classical ligands, a great number of bivalent ligands (i. e. aiming on two distinct OR subtypes), univalent heteromer-selective ligands and bitopic and allosteric ligands have been synthesized The scope of our review is to present the most important of the aforementioned ligands, highlight their

The method has found druggable sites overlapping with the cocrystallized allosteric ligands in 21 GPCR models of these proteins confirms that the same sites can be identified without the presence of bound ligands Results show that for each of the 21 structures with bound ligands there exist many other GPCRs that However, ligands binding at the same location generally show little or no similarity, and the amino acid residues interacting with these ligands also differ.

Rodent models are commonly used to evaluate parathyroid hormone (PTH) and PTH-related protein (PTHrP) ligands identical to the human PTH1R) can lead to differences in receptor-binding and signaling potencies for such ligands

October 2022 Bell-Evans model and steered molecular dynamics in uncovering the dissociation kinetics of ligands We have predicted the absolute ligand residence times on the timescale of seconds. Additionally, we calculated the thermodynamics of ligand binding in terms of ligand binding energies In the experiment, similar sets of residues were found to be in significant contact with both ligands unbinding with the thermodynamics of ligand binding."

We showed a diversity of ligand-free forms of CCR5 at the cell surface constituted of various oligomeric These forms were stabilized differently by distinct ligands.

August 2022 "G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. effects on the cellular signaling from β1-AR to the cAMP response initiated by the three different ligands These data provide insights into the ligand efficacy in the activation of GPCRs and G-proteins."

September 2022 Fly casting with ligand sliding and orientational selection supporting complex formation GA-mD-VcMD is a generalized ensemble method that produces a free-energy landscape of the ligand-receptor Bosentan then slides occasionally from the tip to the root of the N-terminal tail (ligand–sliding). Last, in the pocket, ligand–receptor attractive native contacts are formed. The ligand-sliding corresponds to overcoming of a free-energy barrier between the basins."

central question of GPCR drug discovery is to understand what determines the agonism or antagonism of ligands Ligands exert their action via the interactions in the ligand binding pocket. We hypothesized that there is a common set of receptor interactions made by ligands of diverse structures We computationally docked ~2700 known β2AR ligands to multiple β2AR structures, generating ca 75 000 docking poses and predicted all atomic interactions between the receptor and the ligand.

receptors (aGPCRs) are cell-surface proteins with large extracellular regions that bind to multiple ligands structure revealed that the LK30 binding site on ADGRL3 overlaps with the binding site for an ADGRL3 ligand specifically broke the trans-cellular interaction of ADGRL3 with teneurin, but not with another ADGRL3 ligand Our work provides proof of concept for the modulation of isoform- and ligand specific aGPCR functions

antagonists and rank compounds by offset rate, using rapid calcium assays Potency Is a Ratio of Rates Two ligands The reality is dynamic—ligands arrive, depart, and interact in ways that standard assays often miss.

Genetic variants in ITGA9, which encodes the α9 subunit of integrin α9β1, and SVEP1, a ligand for integrin

September 2022 Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of ligand To understand the basis of the ligand preferences of the receptors and to assist structure-based drug Mutant proteins were assayed to help reveal the basis of ligand specificity, and structural comparison

Furthermore, we found that certain GPCR ligands can regulate GPCR/14-3-3 signals temporally, suggesting