Molecular modeling and site-specific mutagenesis of the histamine-binding site of the histamine H4 receptor.

@article{Shin2002MolecularMA,
  title={Molecular modeling and site-specific mutagenesis of the histamine-binding site of the histamine H4 receptor.},
  author={Niu Shin and Elizabeth Coates and Nicholas Murgolo and K Morse and Marvin L. Bayne and Catherine D. Strader and Frederick J. Monsma},
  journal={Molecular pharmacology},
  year={2002},
  volume={62 1},
  pages={
          38-47
        }
}
The histamine H4 receptor is a novel G-protein-coupled receptor with a unique pharmacological profile. The distribution of H4 mRNA suggests that it may play a role in the regulation of immune function, particularly with respect to allergy and asthma. To define the histamine-binding site of this receptor, molecular modeling and site-directed mutagenesis were used to predict and alter amino acids residing in the histamine-binding pocket. The effects of these alterations on histamine binding and… 

Figures and Tables from this paper

Delineation of Agonist Binding to the Human Histamine H4 Receptor Using Mutational Analysis, Homology Modeling, and ab Initio Calculations

TLDR
The proposed model for agonist binding as well as ab initio calculations for histamine and VUF 8430 explain the observed differences in binding to the H 4R mutants, and provide a molecular understanding for the action of a variety of H 4 receptor-ligands.

Structure- and ligand- based studies to gain insight into the pharmacological implications of histamine H3 receptor

TLDR
A homology model of human histamine H3 receptor was built, and SiteMap was used for the identification of potential binding sites, and a structure-based protein-ligand pharmacophore model with one hydrogen bond donor, one hydrogen Bond acceptor, and one positive ionic feature was developed to validate the 3D pharmacophores hypothesis.

Docking and MD study of histamine H4R based on the crystal structure of H1R.

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

TLDR
The binding mode within this class of structurally highly related compounds and the resulting receptor activation mechanisms are clarified, as Aminopyrimidines, as the most advanced class of hH4R ligands, exhibit remarkable differences in structure–affinity/efficacy relationships.

Generation of a homology model of the human histamine H3 receptor for ligand docking and pharmacophore-based screening

TLDR
A homology model of the hH3R based on the crystal structure of bovine rhodopsin was generated and refined by molecular dynamics simulations in a dipalmitoylphosphatidylcholine)/water membrane mimic before the resulting binding pocket was used for high-throughput docking using the program GOLD.

Cloning and pharmacological characterization of the dog histamine H4 receptor.

Phenylalanine 169 in the Second Extracellular Loop of the Human Histamine H4 Receptor Is Responsible for the Difference in Agonist Binding between Human and Mouse H4 Receptors

TLDR
The results point to an important role of the second extracellular loop in the agonist binding to the H4 receptor and provide a molecular explanation for the species difference between human and mouse H4 receptors.

Chapter 5 Molecular determinants of ligand binding modes in the histamine H 4 receptor : Linking ligand-based 3 D-QSAR models to in silico guided receptor mutagenesis studies Adapted from :

TLDR
The ligand-steered, experimentally supported protein modeling method gives new insights into ligand recognition by H4R and can be used as a general approach to elucidate the structure of protein-ligand complexes.

Structure-based discovery and binding site analysis of histamine receptor ligands

TLDR
The recently solved H1 receptor structure is a major milestone in structure-based drug discovery; however, the analysis demonstrates that for building H3 and H4 receptor homology models, other GPCRs may be more suitable as templates.
...

References

SHOWING 1-10 OF 50 REFERENCES

Molecular basis for the interaction of histamine with the histamine H2 receptor.

Site-directed mutagenesis of the histamine H1-receptor reveals a selective interaction of asparagine207 with subclasses of H1-receptor agonists.

TLDR
It is concluded that different histamine H1-receptor agonists interact in different ways with the H1 -receptor protein and it is speculated that the interaction with the N pi-nitrogen atom is essential for H 1-recept activation.

Unique binding pocket for KW-4679 in the histamine H1 receptor.

Site-directed mutagenesis of the histamine H1 receptor: roles of aspartic acid107, asparagine198 and threonine194.

TLDR
The results show that the histamine H1 receptor recognizes and is activated by histamine through the interactions of Asp107 and the amino group, and Asn198 and the imidazole ring.

Identification of two serine residues involved in agonist activation of the beta-adrenergic receptor.

TLDR
2 serine residues are identified, at positions 204 and 207 in the fifth hydrophobic domain of the beta-adrenergic receptor, which are critical for agonist binding and activation of the receptor.

Identification of residues required for ligand binding to the beta-adrenergic receptor.

TLDR
It is observed that substitution of the proline at position 323 with a serine residue resulted in improper or incomplete processing of the beta AR, presumably reflecting a role for this residue in the folding of the receptor.

Distinct pharmacology of rat and human histamine H3 receptors: role of two amino acids in the third transmembrane domain

TLDR
Starting from the sequence of the human histamine H3 receptor (hH3R) cDNA, the corresponding rat cDNA is cloned and two residues appear to be responsible for the distinct pharmacology of the H3R in the two species.

Mutagenesis of the human 5-HT1B receptor: differences from the closely related 5-HT1A receptor and the role of residue F331 in signal transduction.

TLDR
Results suggest that F331 is involved in the conformational changes necessary for signal transduction of the human 5-HT1B receptor.

Discovery of a novel member of the histamine receptor family.

TLDR
Radioligand binding studies indicated that the H4 receptor has a unique pharmacology and binds [(3)H]histamine and several psychoactive compounds with moderate affinity (K(i) range of 33-750 nM).