scholarly journals Identification of the first surrogate agonists for the G protein-coupled receptor GPR132

RSC Advances ◽  
2015 ◽  
Vol 5 (60) ◽  
pp. 48551-48557 ◽  
Author(s):  
Mohamed A. Shehata ◽  
Hanna Belcik Christensen ◽  
Vignir Isberg ◽  
Daniel Sejer Pedersen ◽  
Andreas Bender ◽  
...  
Keyword(s):  
G Protein ◽  
Binding Mode ◽  
Orphan Receptor ◽  
G Protein Coupled Receptor ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
G Protein Coupled

We report the first pharmacological tool agonist for in vitro characterization of the orphan receptor GPR132, preliminary structure–activity relationships based on 32 analogs and a suggested binding mode from docking.

Structure-activity relationships of agonists for the orphan G protein-coupled receptor GPR27

2021 ◽  
pp. 113777
Author(s):  
Thanigaimalai Pillaiyar ◽  
Francesca Rosato ◽  
Monika Wozniak ◽  
Jeremy Blavier ◽  
Maëlle Charles ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
G Protein Coupled

scholarly journals Novel Agonist Bioisosteres and Common Structure-Activity Relationships for The Orphan G Protein-Coupled Receptor GPR139

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Mohamed A. Shehata ◽  
Anne C. Nøhr ◽  
Delphine Lissa ◽  
Christoph Bisig ◽  
Vignir Isberg ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Structure Activity Relationships ◽  
Common Structure ◽  
Structure Activity ◽  
G Protein Coupled

Structure-activity relationships of imidazothiazinones and analogs as antagonists of the cannabinoid-activated orphan G protein-coupled receptor GPR18

2018 ◽  
Vol 155 ◽  
pp. 381-397 ◽  
Author(s):  
Clara T. Schoeder ◽  
Maria Kaleta ◽  
Andhika B. Mahardhika ◽  
Agnieszka Olejarz-Maciej ◽  
Dorota Łażewska ◽  
...  
Keyword(s):  
G Protein ◽  
G Protein Coupled Receptor ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
G Protein Coupled

scholarly journals Computational Investigations on the Binding Mode of Ligands for the Cannabinoid-Activated G Protein-Coupled Receptor GPR18

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 686 ◽  
Author(s):  
Alexander Neumann ◽  
Viktor Engel ◽  
Andhika B. Mahardhika ◽  
Clara T. Schoeder ◽  
Vigneshwaran Namasivayam ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
G Protein ◽  
Phenyl Ring ◽  
Binding Mode ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Binding Modes ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

GPR18 is an orphan G protein-coupled receptor (GPCR) expressed in cells of the immune system. It is activated by the cannabinoid receptor (CB) agonist ∆9-tetrahydrocannabinol (THC). Several further lipids have been proposed to act as GPR18 agonists, but these results still require unambiguous confirmation. In the present study, we constructed a homology model of the human GPR18 based on an ensemble of three GPCR crystal structures to investigate the binding modes of the agonist THC and the recently reported antagonists which feature an imidazothiazinone core to which a (substituted) phenyl ring is connected via a lipophilic linker. Docking and molecular dynamics simulation studies were performed. As a result, a hydrophobic binding pocket is predicted to accommodate the imidazothiazinone core, while the terminal phenyl ring projects towards an aromatic pocket. Hydrophobic interaction of Cys251 with substituents on the phenyl ring could explain the high potency of the most potent derivatives. Molecular dynamics simulation studies suggest that the binding of imidazothiazinone antagonists stabilizes transmembrane regions TM1, TM6 and TM7 of the receptor through a salt bridge between Asp118 and Lys133. The agonist THC is presumed to bind differently to GPR18 than to the distantly related CB receptors. This study provides insights into the binding mode of GPR18 agonists and antagonists which will facilitate future drug design for this promising potential drug target.

scholarly journals Cutting Edge: Identification of the Orphan Receptor G-Protein-Coupled Receptor 2 as CCR10, a Specific Receptor for the Chemokine ESkine

2000 ◽  
Vol 164 (7) ◽  
pp. 3460-3464 ◽  
Author(s):  
David I. Jarmin ◽  
Miriam Rits ◽  
Dalena Bota ◽  
Norma P. Gerard ◽  
Gerard J. Graham ◽  
...  
Keyword(s):  
G Protein ◽  
Cutting Edge ◽  
Orphan Receptor ◽  
Specific Receptor ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled

scholarly journals Expression, purification, and characterization of the G protein-coupled receptor kinase GRK5.

1994 ◽  
Vol 269 (2) ◽  
pp. 1099-1105 ◽  
Author(s):  
P. Kunapuli ◽  
J.J. Onorato ◽  
M.M. Hosey ◽  
J.L. Benovic
Keyword(s):  
G Protein ◽  
Receptor Kinase ◽  
G Protein Coupled Receptor ◽  
Purification And Characterization ◽  
G Protein Coupled

scholarly journals Characterization of Two Fly LGR (Leucine-Rich Repeat-Containing, G Protein-Coupled Receptor) Proteins Homologous to Vertebrate Glycoprotein Hormone Receptors: Constitutive Activation of Wild-Type Fly LGR1 But Not LGR2 in Transfected Mammalian Cells**This study was supported by NIH Grant HD-23273. The GenBank submission number for fly LGR2 is AF274591.

Endocrinology ◽  
2000 ◽  
Vol 141 (11) ◽  
pp. 4081-4090 ◽  
Author(s):  
Shinya Nishi ◽  
Sheau Yu Hsu ◽  
Karen Zell ◽  
Aaron J. W. Hsueh
Keyword(s):  
G Protein ◽  
Hormone Receptors ◽  
Coupling Mechanism ◽  
Leucine Rich Repeat ◽  
G Protein Coupled Receptor ◽  
Glycoprotein Hormone ◽  
Glycoprotein Hormone Receptors ◽  
Signaling Mechanisms ◽  
G Protein Coupled

Abstract The receptors for lutropin (LH), FSH, and TSH belong to the large G protein-coupled receptor (GPCR) superfamily and are unique in having a large N-terminal extracellular (ecto-) domain important for interactions with the large glycoprotein hormone ligands. Recent studies indicated the evolution of a large family of the leucine-rich repeat-containing, G protein-coupled receptors (LGRs) with at least seven members in mammals. Based on the sequences of mammalian glycoprotein hormone receptors, we have identified a new LGR in Drosophila melanogaster and named it as fly LGR2 to distinguish it from the previously reported fly LH/FSH/TSH receptor (renamed as fly LGR1). Genomic analysis indicated the presence of 10 exons in fly LGR2 as compared with 16 exons in fly LGR1. The deduced fly LGR2 complementary DNA (cDNA) showed 43 and 64% similarity to the fly LGR1 in the ectodomain and transmembrane region, respectively. Comparison of 12 LGRs from diverse species indicated that these proteins can be divided into three subfamilies and fly LGR1 and LGR2 belong to different subfamilies. Potential signaling mechanisms were tested in human 293T cells overexpressing the fly receptors. Of interest, fly LGR1, but not LGR2, showed constitutive activity as reflected by elevated basal cAMP production in transfected cells. The basal activity of fly LGR1 was further augmented following point mutations of key residues in the intracellular loop 3 or transmembrane VI, similar to those found in patients with familial male precocious puberty. The present study reports the cloning of fly LGR2 and indicates that the G protein-coupling mechanism is conserved in fly LGR1 as compared with the mammalian glycoprotein hormone receptors. The characterization of fly receptors with features similar to mammalian glycoprotein hormone receptors allows a better understanding of the evolution of this unique group of GPCRs and future elucidation of their ligand signaling mechanisms.

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