Mapping histamine H4 receptor–ligand binding modes

MedChemComm ◽  
2013 ◽  
Vol 4 (1) ◽  
pp. 193-204 ◽  
Author(s):  
Sabine Schultes ◽  
Saskia Nijmeijer ◽  
Harald Engelhardt ◽  
Albert J. Kooistra ◽  
Henry F. Vischer ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Md Simulation ◽  
Computational Prediction ◽  
G Protein Coupled Receptors ◽  
Simulation Studies ◽  
Binding Modes ◽  
Protein Modelling ◽  
Histamine H4 Receptor ◽  
H4 Receptor ◽  
G Protein Coupled

Computational prediction of ligand binding modes in G protein-coupled receptors (GPCRs) remains a challenging task. Systematic consideration of different protein modelling templates, ligand binding poses, and ligand protonation states in extensive molecular dynamics (MD) simulation studies enabled the prediction of ligand-specific mutation effects in the histamine H4 receptor, a key player in inflammation.

In Silico Characterization of Ligand Binding Modes in the Human Histamine H4 Receptor and their Impact on Receptor Activation

ChemBioChem ◽  
2010 ◽  
Vol 11 (13) ◽  
pp. 1850-1855 ◽  
Author(s):  
Tim Werner ◽  
Kerstin Sander ◽  
Yusuf Tanrikulu ◽  
Tim Kottke ◽  
Ewgenij Proschak ◽  
...  
Keyword(s):  
Ligand Binding ◽  
In Silico ◽  
Receptor Activation ◽  
Binding Modes ◽  
Histamine H4 Receptor ◽  
H4 Receptor ◽  
In Silico Characterization ◽  
Human Histamine

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 Enigmatic Histamine Receptor H4 for Potential Treatment of Multiple Inflammatory, Autoimmune, and Related Diseases

Life ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 50
Author(s):  
Pakhuri Mehta ◽  
Przemysław Miszta ◽  
Przemysław Rzodkiewicz ◽  
Olga Michalak ◽  
Piotr Krzeczyński ◽  
...  
Keyword(s):  
Cell Activation ◽  
Histamine Receptor ◽  
Mast Cell Activation ◽  
Histamine H4 Receptor ◽  
Inflammatory Models ◽  
The Family ◽  
Cellular Pathways ◽  
H4 Receptor ◽  
G Protein Coupled

The histamine H4 receptor, belonging to the family of G-protein coupled receptors, is an increasingly attractive drug target. It plays an indispensable role in many cellular pathways, and numerous H4R ligands are being studied for the treatment of several inflammatory, allergic, and autoimmune disorders, including pulmonary fibrosis. Activation of H4R is involved in cytokine production and mediates mast cell activation and eosinophil chemotaxis. The importance of this receptor has also been shown in inflammatory models: peritonitis, respiratory tract inflammation, colitis, osteoarthritis, and rheumatoid arthritis. Recent studies suggest that H4R acts as a modulator in cancer, neuropathic pain, vestibular disorders, and type-2 diabetes, however, its role is still not fully understood.

Multiparametric Homogeneous Method for Identification of Ligand Binding to G Protein-Coupled Receptors: Receptor–Ligand Binding and β-Arrestin Assay

2013 ◽  
Vol 85 (4) ◽  
pp. 2276-2281 ◽  
Author(s):  
Kari Kopra ◽  
Markus Kainulainen ◽  
Piia Mikkonen ◽  
Anita Rozwandowicz-Jansen ◽  
Pekka Hänninen ◽  
...  
Keyword(s):  
Ligand Binding ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Receptor Ligand ◽  
Homogeneous Method ◽  
G Protein Coupled

scholarly journals Structure-based virtual screening for fragment-like ligands of the G protein-coupled histamine H4 receptor

MedChemComm ◽  
2015 ◽  
Vol 6 (6) ◽  
pp. 1003-1017 ◽  
Author(s):  
Enade P. Istyastono ◽  
Albert J. Kooistra ◽  
Henry F. Vischer ◽  
Martien Kuijer ◽  
Luc Roumen ◽  
...  
Keyword(s):  
Virtual Screening ◽  
G Protein ◽  
Histamine H4 Receptor ◽  
H4 Receptor ◽  
G Protein Coupled ◽  
Homology Models

Structure-based virtual screening using H1R- and β2R-based histamine H4R homology models identified 9 fragments with an affinity ranging from 0.14 to 6.3 μm for H4R.

Family Resemblances? Ligand Binding and Activation of Family A and B G-Protein-Coupled Receptors

2007 ◽  
Vol 35 (4) ◽  
pp. 707-708 ◽  
Author(s):  
D.R. Poyner ◽  
M. Wheatley
Keyword(s):  
Ligand Binding ◽  
G Protein ◽  
Present Article ◽  
G Protein Coupled Receptors ◽  
Society Meeting ◽  
Family Resemblances ◽  
G Protein Coupled ◽  
Compare And Contrast ◽  
Present Meeting

In April 2007, the Biochemical Society held a meeting to compare and contrast ligand binding and activation of Family A and B GPCRs (G-protein-coupled receptors). Being the largest class, Family A GPCRs usually receive the most attention, although a previous Biochemical Society meeting has focused on Family B GPCRs. The aim of the present meeting was to bring researchers of both families together in order to identify commonalities between the two. The present article introduces the proceedings of the meeting, briefly commenting on the focus of each of the following articles.

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