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Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions
The high-resolution structure of a stabilized version of the human A2Aadenosine receptor (A2AAR) reveals the position of about 60 internal waters, which suggests an almost continuous channel in the GPCR and can explain the allosteric effects of Na+ on ligand binding and how cholesterol may contribute to G PCR stabilization.
Structure of CC Chemokine Receptor 2 with Orthosteric and Allosteric Antagonists
The present structure of CCR2 in a ternary complex with an orthosteric and allosteric (CCR2-RA-[R]) antagonist suggests diverse pocket epitopes that can be exploited to overcome obstacles in drug design.
Controlling the Dissociation of Ligands from the Adenosine A2A Receptor through Modulation of Salt Bridge Strength.
Light is shed on a structural determinant of ligand dissociation kinetics and a means by which this property may be optimized in G protein-coupled receptors.
The role of a sodium ion binding site in the allosteric modulation of the A(2A) adenosine G protein-coupled receptor.
Drug‐Target Residence Time—A Case for G Protein‐Coupled Receptors
It is proposed that drug‐target RT should be taken into account as an additional parameter in the lead selection and optimization process, which should ultimately lead to an increased number of candidate drugs moving to the preclinical development phase and on to the market.
Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity
- Marjolein Soethoudt, U. Grether, M. van der Stelt
- Biology, ChemistryNature communications
- 3 January 2017
The most extensive characterization of the molecular pharmacology of the most widely used CB2R ligands to date is reported, identifying marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects.
Bias in chemokine receptor signalling.
Kinetics for Drug Discovery: an industry-driven effort to target drug residence time.
G protein‐coupled receptors of the hypothalamic–pituitary–gonadal axis: A case for gnrh, LH, FSH, and GPR54 receptor ligands
The small molecule agonists and antagonists that are currently being developed to intervene with the action of four receptors, including GnRH receptors, LH receptor, FSH receptor and LH receptor are discussed.
Molecular Basis of Ligand Dissociation from the Adenosine A2A Receptor
It is suggested that the antagonist ZM241385 follows a multistep dissociation pathway, consecutively interacting with distinct receptor regions, a mechanism that may also be common to many other GPCRs.