Effect of Ions and Sequence Variants on the Antagonist Binding Properties of the Histamine H₁ Receptor.

ABSTRACT: The histamine H₁ receptor (H₁R) is a G protein-coupled receptor (GPCR) and represents a main target in the treatment of allergic reactions as well as inflammatory reactions and depressions. Although the overall effect of antagonists on H₁ function has been extensively investigated, rather little is known about the potential modulatory effect of ions or sequence variants on antagonist binding. We investigated the dynamics of a phosphate ion present in the crystal structure and of a sodium ion, for which we determined the position in the allosteric pocket by metadynamics simulations. Both types of ions exhibit significant dynamics within their binding site; however, some key contacts remain stable over the simulation time, which might be exploited to develop

SUBMITTER: Conrad M 

PROVIDER: S-EPMC8836275 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature